Development Of Autonomic Dysfunction Research Articles

Зв’язок реологічних властивостей сироватки крові зі станом вегетативної нервової системи при ревматоїдному артриті

Актуальність. Ревматоїдний артрит (РА) належить до найбільш частих запальних хвороб суглобів, і численність таких пацієнтів всюди збільшується, завдаючи величезного медико-соціального й економічного збитку. Важлива роль у патогенезі РА відводиться порушенням функції вегетативної нервової системи (ВНС), стан якої тісно пов’язаний із реологічними властивостями сироватки крові (РВСК). Мета дослідження: оцінити співвідношення «вегетативного паспорта» хворих на РА і вегетативної дисфункції з РВСК при різних варіантах перебігу хвороби. Матеріали та методи. Обстежено 173 хворих на РА у віці від 18 до 79 років (в середньому 46 років), серед яких було 21 % чоловіків та 79 % жінок. Тривалість маніфестації захворювання становила 10 років, серопозитивний за ревматоїдним фактором і антицитруліновими антитілами варіант РА встановлено в 3/4 випадків, позасуглобову (системну) форму хвороби діагностовано в 37 % спостережень. З використанням комп’ютерного тензіометру «PAT2-Sinterface» (Німеччина) визначали поверхневі показники сироватки крові — в’язкість, пружність, натяг, релаксацію й модуль в’язкоеластичності. Результати. «Вегетативний паспорт» визначав інтегральні клініко-лабораторні та інструментальні ознаки РА, при цьому тяжкість вегетативної дисфункції прямо корелювала з темпами прогресування патології суглобів, а у симпатотоніків — з початковими параметрами ревматоїдного фактора в крові й ступенем активності РА. Зміни РВСК супроводжувались збільшенням рівноважного (статичного) поверхневого натягу, що реєструвалося в 70 % випадків. Інтегральний стан міжфазної активності, релаксаційних та в’язкоеластичних характеристик крові визначав тип ВНС і наявність у хворих вегетативної дисфункції (ваготонікам властиві підвищення модуля в’язкоеластичності й зниження поверхневого натягу, симпатотонікам — підвищення поверхневого натягу та зниження поверхневої в’язкості). Параметри РВСК пов’язані з вираженістю вегетативних розладів, а показник поверхневої в’язкості має прогностичну значущість. Висновки. Розвиток вегетативної дисфункції пов’язаний не лише з особливостями перебігу суглобового синдрому і екстраартикулярних ознак РА, а й зі станом ВНС, що бере участь в порушеннях РВСК. У майбутньому буде корисною оцінка стану ВНС для подальших своєчасних реабілітаційних заходів щодо захворювання.

The state of vegetative regulatory systems of pupils with different academic performance

The transition to primary school requires pupils to adapt to new conditions of the educational environment, accompanied by the use of physiological reserves of the body. School stress can hinder the academic success of children and adolescents, creative solutions to complex and new problems, which, in turn, can lead to underestimation of abilities and underestimation of pupils self-esteem. Chronic exposure to academic stress can lead to school burnout and the formation of psychosomatic disorders. The aim of the study was to compare the functional state of autonomic regulatory systems among pupils with different levels of academic achievement. 60 children (10-13 years old) took part in the longitudinal study. The functional state of the autonomic regulatory systems was determined by analyzing 5-minute recordings of the electrocardiogram in a state of quiet wakefulness with eyes closed in a sitting position. Pupils were divided into 3 groups depending on the level of their academic performance, which was determined by the average score of 8 basic subjects. Statistical data processing was performed using the Mann-Whitney, Kraskell-Wallis, Dunnett, Fisher’s φ-test. Significant differences in heart rate variability (HRV) parameters depending on the level of academic achievement were found only in the 5th and 6th years of study, which reflected the different physiological cost of adaptation to primary school. The vegetative profile of pupils with academic performance lower than the average in the 5th year of study indicated overstrain of regulatory systems and fatigue. Among pupils with academic performance higher than the average in the 6th year of study 2.4 times more often than pupils with average academic performance, the optimal state of autonomic regulatory systems was observed (respectively, 46.2% and 19.1%, p≤0,05), and in the 7th year of study – 2.5 times compared to pupils with academic performance below average (respectively, 46.2% and 18.2%, p≤0.05), which may indicate a higher physiological price for adaptation to primary school pupils with academic performance below average. Fatigue and overexertion of the mechanisms of autonomic regulation are characteristic of pupils with academic performance below average, while pupils with academic performance above average had a high level of stress adaptive-compensatory mechanisms in the 6th year of study. The category of pupils with a level of academic performance below average should be assigned to the risk group in terms of the development of autonomic dysfunction and psychosomatic diseases.

Predictors of autonomic dysfunction among predialysis chronic kidney disease patients in Nigeria.

Chronic kidney disease (CKD) is a global public health problem with increasing incidence and mortality in Africa. Autonomic dysfunction (AD) has been implicated as a major contributor to the disease morbidity and mortality, but little is known about the predictors of this dysfunction in African populations. Understanding the predictors of this condition is necessary for early detection and management of CKDs. Objectives: This study was designed to determine the predictors of AD in CKD patients in Nigeria. It was a cross-sectional study of CKD patients at University of Nigeria Teaching Hospital, Enugu, Nigeria. The CKD patients with AD were compared with those without AD and a normal control group. Autonomic function was assessed through noninvasive cardiovascular tests: measurement of resting tachycardia, orthostatic hypotension, heart rate response (HRR) to standing, HRR to Valsalva maneuvre, and HRR to respiration. Data on symptoms of CKD and AD were obtained using a validated questionnaire. The mean age of the CKD patients was 41.3 ± 1.5 (range: 21-69) years. Early hospital presentation is associated with significantly less risk of the development of AD (P < 0.001). Dizziness, nocturnal diarrhea, and impotence are the major markers/predictors of AD in CKD patients (P < 0.05). AD is common among predialysis CKD patients in Nigeria, and best predicted by the presence of postural dizziness, nocturnal diarrhea, and impotence in men. Physicians should, therefore, be on the lookout for these features for prompt and adequate management of cases.

Association of Autonomic Dysfunction With Disease Progression and Survival in Parkinson Disease

Evidence suggests that development of autonomic dysfunction (AutD) may negatively affect disease course and survival in patients with synucleinopathies. However, the few available studies on Parkinson disease (PD) have conflicting results, comprise a small number of patients, have short follow-up periods, and lack pathologic confirmation of the diagnosis. To examine the association of time of onset of AutD with disease progression and survival in PD. This retrospective review of clinical data from 100 consecutive patients with an autopsy-confirmed diagnosis of PD from the archives of the Queen Square Brain Bank in London, United Kingdom, from January 1, 2006, to June 3, 2016, included patients with PD regularly seen by hospital specialists (neurologists or geriatricians) in the United Kingdom throughout their disease until death. Patients with dementia before or within 1 year after onset of motor symptoms, monogenic forms of PD, comorbidities that affect autonomic function, a coexisting neuropathologic diagnosis, or insufficient clinical information were excluded. Survival and time from diagnosis to specific disease milestones were calculated to assess disease progression. Autonomic dysfunction was defined as autonomic failure at autonomic function testing or 2 of the following symptoms: urinary symptoms, constipation, upper gastrointestinal tract dysfunction, orthostatic hypotension, sweating abnormalities, or erectile dysfunction. Multivariable Cox proportional hazards regression models on the risk of a disease milestone and death were used. A total of 100 patients (60 [60.0%] male; mean [SD] age at diagnosis, 63.9 [10.3] years; mean [SD] disease duration, 14.6 [7.7] years) were studied. Autonomic dysfunction developed in 85 patients (mean [SD] time from diagnosis, 6.7 [7.7] years) and was associated with older age at diagnosis, male sex, poor initial levodopa treatment response, and postural instability and gait difficulty motor PD subtype in linear regression analysis, but staging of α-synuclein pathologic changes was unrelated. Earlier AutD increased the risk of reaching the first milestone (hazard ratio, 0.86; 95% CI, 0.83-0.89; P < .001) and shortened survival (hazard ratio, 0.92; 95% CI, 0.88-0.96; P < .001). Older age at diagnosis and poorer levodopa treatment response were the other factors associated with shorter survival in adjusted multivariate analysis. Earlier AutD is associated with a more rapid development of disease milestones and shorter survival in patients with PD.

Abstract P119: Association Between Inspiratory Muscle Strength and Sympathetic Cardiac Modulation and Baroreflex in Patients With End Stage Renal Disease Undergoing Hemodialysis

Introduction: Patients with end-stage renal disease (ESRD) are susceptible to development of autonomic dysfunction and have metabolic and muscular changes which are associated with decreased functional capacity. Objectives: To evaluate respiratory muscle strength and cardiac autonomic modulation in ESRD patients undergoing hemodialysis. Methods: ESRD patients undergoing hemodialysis (n= 9, mean age 46.2±14.1 years) and healthy controls (n =7, mean age 44.6±14.6 years) were assessed. Non–invasive curves of blood pressure were recorded continuously (Finometer ®) for 10 minutes. The heart rate variability was estimated in the time and frequency domain. Inspiratory and expiratory maximal pressures (IPmax and EPmax) were quantified using a pressure transducer. Mann-Whitney and Spearman tests were used. The results were expressed as mean ± SD. Results: Regarding respiratory muscle strength, ESRD patients had lower inspiratory (IPmax: 79.1±25.0 vs 121.3±24.3cmH 2 O, p=0.03) and expiratory muscle strength (EPmax 92.8±23.1 vs 153.8±23.5cmH 2 O, p=0.01) then healthy controls. ESRD patients presented lower heart rate variability than healthy controls (SDNN: 19.2±4.0 vs 52.6±18.8ms, p=0.000) and lower RMSSD, an index of vagal modulation (11.8±5.2 vs 46.1±20.4ms, p=0.000). Regarding frequency domain indexes, ESRD patients presented higher low-frequency component (LFnu= 68.9±11.9 vs 47.3± 2.8, p=0.008), lower high-frequency component (HFnu= 31.1±11.9 vs 52.7±12.8, p=0.008) and higher sympathovagal balance (LF/HF: (LF/HF= 3.1±1.3 vs 1.1±0.5, p=0.005) when compared to controls. Furthermore baroreflex sensitivity was reduced in ESRD patients (alfa index: 3.6±1.6 vs 11.7±4.4ms/mmHg, p=0.002). In ESRD patients the IPmax was significantly associated with LF (r=-0.813, p=0.014) and with alfa index (r=-0.900, p=0.037). Conclusion: ESRD patients undergoing hemodialysis presented reduced inspiratory muscle strength, increased sympathetic modulation and reduced cardiac vagal modulation and impaired baroreflex sensitivity. In these patients inspiratory muscle strength was associated with sympathetic cardiac modulation and baroreflex.

Reorganisation of the Autonomic Nervous System

Canada Spinal cord injury (SCI) results not only in a devastating paralysis but is also associated with a myriad of secondary conditions including autonomic dysfunctions [1]. For example cardiovascular responses to orthostatic challenge and exercise following SCI are significantly altered. When able-bodied individual assumes standing position a typical blood pressure response associated with redistribution of blood within the body and approximately 500 ml transfers caudally to the abdominal and lower extremities vasculature. This typically associated with central baroreceptors activation, decreasing vagal tone to the heart, and increasing in peripheral sympathetic activity. The increase in sympathetic tone with standing result in increased heart rate and peripheral vasoconstriction that responsible in maintenance of stable level of arterial blood pressure. After SCI, although the baroreceptors certainly detect reductions in central blood volume during orthostatic stress, disrupted descending spinal sympathetic pathways precludes the capacity for the peripheral vasoconstriction, often resulting in abnormal fluctuation in blood pressure with changing position by individuals with SCI. Latest evidence from preclinical studies and clinical evaluations of individuals with SCI demonstrated that disruption of autonomic spinal pathways and plastic alterations within the spinal cord and periphery that occur after SCI are among the leading causes for the dysfunctional cardiovascular control affecting both: 1) the heart, and 2) the systemic vasculature. Cardiac function is under the combined control of sympathetic (SPNs from T1-T5 levels) and parasympathetic vagal divisions of autonomic nervous systems. After a cervical SCI, sympathetic tonic control is disrupted, while vagal control is intact. Alternatively, when the SCI is below the T6 level, both sympathetic and vagal control of the heart is intact. These divergent scenarios of cardiac autonomic control lead to quite different cardiovascular responses in various physiological circumstances such as rest, exercise, or orthostatic challenge [2]. It is not just the heart that can have these differing autonomic effects (i.e., disrupted sympathetic control yet intact parasympathetic pathways). These same considerations have important outcomes for a variety of essential functions including the cerebrovasculature, urinary bladder, bowel, temperature and sweat glands control. We are just beginning to unravel the mechanisms underlying abnormal cardiovascular function after SCI. The morphological changes within the spinal autonomic circuits after SCI have been established relatively recently. [3] Furthermore, the role these changes are playing in the development of autonomic dysfunction has only just been solidified. A variety of autonomic circuits have been highlighted that possibly contribute to abnormal cardiovascular control after SCI. The disruption of descending spinal cardiovascular pathways leads to a minimum of six neuroanatomical changes that influence autonomic cardiovascular control:

14 * Acute and chronic withdrawal of dorsal vagal preganglionic activity in the central nervous system predisposes to ventricular arrhythmia

Introduction: Electrical stimulation of the vagus nerve has been shown to protect against ventricular tachyarrhythmia (VT). The exact mechanism of this effect is unknown and it also remains unclear whether acute or chronic withdrawal of tonic vagal efferent activity to the heart predisposes the heart to VT. To investigate this, we acutely silenced the vagal preganglionic neurones in the dorsal motor nucleus of the vagus nerve (DVMN) in a rat model using a pharmogenetic approach, and we used the triple-synuclein-null mice as a model of autonomic dysfunction associated with chronic reduction of vagal tone. Methods: In 12 male Sprague-Dawley rats (380-420g), lentiviral vectors were used to transduce DVMN neurones to express an inhibitory Gi-protein-coupled Drosophila allatostatin receptor (AlstR) or green fluorescent protein as a control. Application of a natural ligand of AlstR - an insect peptide allatostatin (5 µl) produces selective and rapid silencing of targeted neurones. To investigate the role of age-dependent autonomic dysfunction, 7 young (2-3 months) and 8 old (12-16 months) wild type (WT) and triple-synuclein-null (TKO) mice were studied. The animals underwent programmed electrical stimulation of the right ventricle under urethane anaesthesia (1.3g/kg) to obtain ventricular effective refractory period (VERP). Ventricular tachycardia (VT) inducibility by burst pacing was also assessed in the acute rat models. Results: Acute inhibition of the DVMN vagal preganglionic neurones in rats resulted in shortening of the VERP (32.6±0.8 vs 41.5±0.5 ms; p=0.002) and lowered VT threshold on burst pacing (21.7±4.2 vs 44.4±8.9 Hz; p=0.043). Young TKO mice showed no difference in VERP (37.0±5.2 vs 37.0±3.1 ms). However, development of autonomic dysfunction in older TKO mice was associated with a reduction in VERP (30.6±2.3 vs 43.4±2.3 ms; p=0.003). In old WT animals, systemic administration of methylatropine (2mg/kg) mimicked the pro-arrhythmic phenotype of synuclein deficiency with significant VERP shortening (31.0±2.6 vs 43.4±2.3 ms; p=0.004). Conclusion: This study demonstrates that both acute and chronic decrease in activity of a distinct population of vagal preganglionic neurones in the DVMN predisposes the heart to ventricular arrhythmia by reduction of the effective refractory period. CNS disorders associated with autonomic dysfunction (mimicked here by synuclein deficiency) and decreased DVMN activity may lead to pro-arrhythmic phenotype.

Association of Autoimmunity to Autonomic Nervous Structures With Nerve Function in Patients With Type 1 Diabetes: A 16-Year Prospective Study

OBJECTIVE We prospectively evaluated the association between autoimmunity to autonomic nervous structures and autonomic neuropathy in type 1 diabetes in relation to clinical variables. RESEARCH DESIGN AND METHODS A cohort of 112 patients with type 1 diabetes was prospectively followed from adolescence (T0) to approximately 4 (T4) and 16 (T16) years later. Standard cardiovascular (CV) tests and neurological examination were performed and related to the presence of circulating antibodies (Ab) to autonomic nervous structures detected at T0 and T4. Quality of life was assessed by a diabetes-specific questionnaire. RESULTS Sixty-six patients (59% of the cohort) were reexamined at T16 (age 31.4 ± 2 years; disease duration 23.4 ± 3.7 years). Nineteen had circulating Ab to autonomic structures. Prevalence of abnormal tests and autonomic symptoms were higher in Ab-positive (68 and 26%, respectively) than Ab-negative (32 and 4%) patients (P < 0.05). Among Ab-positive patients, the relative risk (RR) of having at least one altered CV test was 5.77 (95% CI 1.56-21.33), and an altered deep breathing (DB) test (<15 bpm) was 14.65 (2.48-86.46). Previous glycemic control was the only other predictor (RR 1.06 [1.002-1.13]/mmol/mol HbA1c increase). Presence of Ab carried over a 68% probability of developing an altered CV test; absence of Ab carried a 91% probability of not having an altered DB test and an 89% probability of not having an altered Valsalva ratio. Autonomic neuropathy was independently associated with worse quality of life. CONCLUSIONS Circulating Ab to autonomic structures are associated with the development of autonomic dysfunction in young diabetic patients independent of glycemic control.

Autonomic dysfunction in muscular dystrophy: a theoretical framework for muscle reflex involvement

Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

Abstract 498: Increased Blood Pressure Variability and Baroreflex Impairment in Patients With End-stage Renal Disease Undergoing Hemodialysis

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis are susceptible to the development of autonomic dysfunction, which is associated with an increased risk of sudden death. Experimental and clinical evidence suggest a crucial role of autonomic dysfunction for both, the progression of renal disease and for the high rate of cardiovascular events in these patients. In the present study, we evaluated the heart rate variability (HRV), the blood pressure variability (BPV) and the baroreflex sensitivity (BRS) in ESRD patients undergoing hemodialysis and normal controls. Methods: Nine ESRD patients undergoing hemodialysis (mean age 53.4±10.2 years, 4 male) and nine age-matched healthy controls (mean age 52.8±10.2 years, 4 male) were assessed. Non−invasive curves of blood pressure (BP) were recorded continuously (Finometer ®) for 10 minutes, at rest, in the supine position. The heart rate variability (HRV) and systolic blood pressure variability (BPV) were estimated in the time and frequency domain (spectral analysis). The BRS was quantified by alpha index. Statistical analyzes were performed by Student's t test and the results were expressed as mean ± standard deviation. Results: ESRD patients presented lower HRV in time domain than healthy controls (SDNN: 25.8±10.7 vs. 44.6±11.7 ms, p&lt;0.01; VAR NN: 768.3±607.4 vs. 2113.9±1261.6 ms 2 , p=0.01). All frequency domain analyzed indexes, i.e., total power (361.9±297.0 vs. 1227.2±696.3 ms 2 , p&lt;0.01), high-frequency (181.8±128.7 vs. 358.7±179.8 ms 2 , p=0.047), low-frequency (55.1±44.2 vs. 444.6±389.9 ms 2 , p=0.02) and very-low-frequency (72.5±75.1 vs. 279.2±119.5 ms 2 , p&lt;0.01) of HRV were lower in ESRD patients. The BPV was higher in ESRD patients when compared to controls (VAR PAS: 98.4±72.0 vs. 35.4±21.4 ms 2 , p=0.03) and BRS was lower in ESRD patients (alpha index: 4.34±3.05 vs. 7.56±2.50 ms/mmHg, p&lt;0.02). Conclusion: ESRD patients undergoing hemodialysis presents reduced HRV, increase in BPV and reduced baroreflex sensitivity. These impairments may be associated with mortality in ESRD.

Assessment of autonomic dysfunction of multiple system atrophy with laryngeal abductor paralysis as an early manifestation

Laryngeal abductor palsy (LAP) is common in the advanced stages of multiple system atrophy (MSA). However, occurrence of LAP in the early stages might make a diagnosis of MSA difficult. To search for a clue to diagnosis of MSA with LAP as an early manifestation, we assessed the clinical features of autonomic dysfunction and the central cardiovascular control circuits in two MSA patients who had LAP as a cardinal symptom in the early stages. Development of autonomic dysfunction was preceded or followed by LAP. The autonomic symptom occurring predominantly in the earliest stages was urinary disturbance rather than orthostatic hypotension. Although screening cardiovascular autonomic function tests did not conclusively indicate a diagnosis of MSA, vasopressin release in response to head-up tilt and growth hormone response to clonidine administration demonstrated inappropriate responses, suggesting that the noradrenergic neurons of the caudal ventrolateral medulla were impaired. Diagnosis of atypical MSA with LAP in the early stages might be accelerated by a detailed investigation focused on urinary symptoms and neuroendocrine approaches.

Stiff-man syndrome: from the bedside to the bench.

The study of SMS, a rare disease, has resulted in a better understanding of a more common disorder, IDDM, and has allowed investigators to gain insights into the molecular mechanisms of autoimmunity. Many unanswered questions remain, such as the specific site of disease activity in SMS, both at the bedside (cortex, brain stem, or spinal cord) and at the bench (neuronal cytoplasma or synapse). The association of SMS with neoplastic disease and the development of autonomicdysfunction are not understood. The next decade may provide answers to these puzzling issues.

Neurophysiological mechanisms of neurological disorders in people irradiated in the Chernobyl’ catastrophe

We analyzed shifts in the functional parameters of the autonomic and segmental somatic reflex mechanisms in various categories of people subjected to irradiation because of the catastrophe at the Chernobyl’ NPS. It is demonstrated that long-lasting irradiation even with mild intensity evokes serious damage to the central structures controlling autonomic functions (first of all, the hypothalamus). This results in the development of autonomic dysfunction with domination of disorders of the sympathetic system manifested in a dramatic drop in the amplitude, an increase in the duration, and modification of the phase structure of evoked autonomic skin responses in all examined groups of persons. Cardiovascular and neurotrophic disorders are crucial factors, which determine pathological modifications in the somatic reflex sphere (a drop in the amplitude of sensory evoked potentials and a decrease of the conduction velocity in the peripheral nerves, a drop in the amplitude of M responses in the limb muscles, but with relatively small shifts in the synaptic relays of segmental reflex arcs).

Differential diagnosis of parkinsonism with [18F]fluorodeoxyglucose and PET.

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders (APD) is complicated by the presence of signs and symptoms common to both forms of parkinsonism. Metabolic brain imaging with [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be a useful adjunct in differentiating APD from IPD. To explore this possibility, we studied 48 parkinsonian patients suspected as having possible APD because of a deteriorating response to dopaminergic treatment, the development of autonomic dysfunction, or both. A group of 56 patients with likely IPD served as control subjects. We used quantitative FDG/PET to measure regional rates of cerebral glucose use in IPD and APD patients. We used discriminant analysis to categorize IPD and APD patients based on their regional metabolic data. We found that a linear combination of caudate, lentiform, and thalamic values accurately discriminated APD from IPD patients (p < 0.0001). Significant metabolic abnormalities were present in the striatum and the thalamus of 36 of 48 (75%) APD patients. Our findings show that measurements of regional glucose metabolism can be used to discriminate patients with suspected APD from their counterparts with classic IPD. FDG/PET may be a useful adjunct to the clinical examination in the differential diagnosis of parkinsonism.

An Investigation of Antibodies to Nerve Growth Factor in Diabetic Autonomic Neuropathy

Nerve growth factor (NGF) is required for development and maintenance of autonomic nervous function and is highly expressed in the iris. An association between sensory and autonomic diabetic neuropathy and NGF function has been postulated. In light of the evidence for an autoimmune component to the pathogenesis of autonomic neuropathy in Type 1 diabetes mellitus, an enzyme linked immunosorbent assay (ELISA) was established to investigate the presence of autoantibodies to mNGF in: 20 patients with long-standing Type 1 diabetes with abnormal autonomic function tests, of whom 14 had symptomatic autonomic neuropathy, 3 had an episode of iritis, and 6 had no autonomic symptoms; 9 age-matched patients with Type 1 diabetes and no complications; 10 healthy control subjects. Insulin antibodies by ELISA and autoantibodies to other endocrine targets were also measured. The specificity of anti-mNGF autoantibody ELISA was further confirmed by immunodepletion on mNGF-Sepharose 4B. No differences in antibody binding to mNGF were detected, between any of the patient groups and control subjects. There was no relationship between age, sex, and diabetes duration and mNGF binding. High levels of anti-mNGF autoantibodies were found in only one diabetic patient who had no evidence of neuropathy, raising the possibility that an autoimmune component to NGF might precede the development of autonomic dysfunction. It remains to be established whether autoantibodies to NGF play a role in diabetic autonomic neuropathy and prospective studies will be required to investigate whether the autoantibodies are a feature of evolving but not established neuropathy.