Poincaré plot width, morning urine norepinephrine levels, and autonomic imbalance in children with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) in childhood is accompanied by sympathetic overflow unopposed by the parasympathetic tone. Complex methods like power spectral analysis of heart rate variability have been applied to study this imbalance. In this report, width of Poincaré scattergram of the R-R interval (parasympathetic tone) and morning urine norepinephrine concentration (sympathetic activity) were used to assess autonomic imbalance. METHODS: Poincaré plot was obtained from the electrocardiographic channel of nocturnal polysomnography and its width was measured, and norepinephrine-to-creatinine concentration ratio was calculated in morning urine specimen. RESULTS: Twenty children with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia (oxygen saturation of hemoglobin [SpO(2)] nadir <90%), 24 subjects with mild hypoxemia (SpO(2) nadir ≥90%), and 11 control subjects were recruited. Children with obstructive sleep apnea and moderate-to-severe hypoxemia had significantly narrower Poincaré plot width (318.7 ± 139.3 ms) and higher ln-transformed urine norepinephrine-to-creatinine ratio (4.5 ± 0.6) than control subjects (484.2 ± 104.4 ms and 3.8 ± 0.4, respectively; P < 0.05). Ln-transformed urine norepinephrine levels were inversely related to Poincaré plot width (P = 0.02). CONCLUSIONS: Subjects with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia have enhanced sympathetic activity and reduced parasympathetic drive. Poincaré plot width and urine norepinephrine levels are simple measures of autonomic imbalance in pediatric obstructive sleep apnea.

Association of aryl hydrocarbon receptor gene polymorphism with the neurobehavioral function and autonomic nervous system function changes induced by benzo[a]pyrene exposure in coke oven workers.

OBJECTIVE: To analyze the association of aryl hydrocarbon receptor (AhR) gene polymorphism and the neurotoxicity induced by benzo[a]pyrene (B[a]P) in coke oven workers. METHODS: Subjects, 214 coke oven workers and 81 controls, were detected for neurobehavioral function and autonomic nervous system (ANS) function. Airborne B[a]P concentration, urinary 1-hydroxypyrene level, and AhR gene polymorphisms were determined and analyzed for their association with B[a]P neurotoxicity. RESULTS: Neurobehavioral function and ANS function were significantly decreased and dependent on B[a]P dose. The AhR GG, GA, and AA genotypes in G1661A fitted the Hardy-Weinberg equation, whereas C1549T and G1708A gene mutants were not detected. Indices indicating neurotoxicity showed no significant difference among individuals with AA, GG, or GA genotype except for the confusion-bewilderment (P > 0.05). CONCLUSION: The AhR gene polymorphism is not thought to correlate with B[a]P neurotoxicity among coke oven workers.

Increased sympathetic activity in children with obstructive sleep apnea: cardiovascular implications.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased sympathetic activity and hypertension in adults. We tested the hypothesis that children with OSA also have increased sympathetic activity as measured by overnight urinary catecholamines, and that this increase is related to the severity of OSA and to blood pressure (BP). METHODS: Seventy snoring children referred for assessment of sleep disordered breathing and 26 healthy non-snoring control children (age range: 3-12 years, 59 M/37 F) were studied. Overnight polysomnography was performed coincident with a 12h overnight urine collection. Urinary catecholamine levels were determined using high performance liquid chromatography (noradrenaline, adrenaline and dopamine, with levels adjusted for creatinine excretion). Simple linear and stepwise multiple linear regressions were used to determine the independent associations between catecholamine levels and age, gender, BMI z-score, systolic BP z-score, diastolic BP z-score, and apnea hypopnea index (AHI). RESULTS: Simple linear regressions revealed significant associations between noradrenaline and AHI (r = 0.32) and age (r = -0.20, p < 0.05 for both). Significant associations were also found between adrenaline and AHI (r = 0.27) and age (r = -0.25, p < 0.05 for both). Systolic BP z-score and diastolic z-score were both significantly associated with adrenaline (r = 0.22 and r = 0.20 respectively, p < 0.05 for both). Multivariate analysis revealed that only AHI was a significant independent predictor of noradrenaline (model R(2) = 0.10, p = 0.001). Similarly, only AHI and age were significant independent predictors of adrenaline (model R(2) = 0.12, p < 0.05). CONCLUSIONS: This study demonstrates that levels of overnight urinary noradrenaline and adrenaline are related to the severity of OSA in children. These data indicate that children with OSA have increased sympathetic tone that may contribute to the cardiovascular consequences of the condition.

[The assessment of 24-hour ambulatory blood pressure monitoring (ABPM), microalbuminuria and diabetic autonomous neuropathy in children with type 1 diabetes and hypertension]. / Ocena 24-godzinnego monitorowania cisnienia tetniczego, mikroalbuminurii oraz autonomicznej neuropatii cukrzycowej u dzieci z cukrzyca typu 1 i nadcisnieniem tetniczym.

INTRODUCTION: The late complications of diabetes consisted of autonomic neuropathy, nephropathy, which more often coexist with hypertension in children with type 1 diabetes mellitus. THE AIM OF THE STUDY was to assess the connections between changes in the autonomous nervous system, 24-hour ABPM and daily albumin excrection in children with hypertension and type 1 diabetes mellitus. MATERIAL: The group consisted of 72 patients with diabetes (diabetes duration time 6.5+/-1.5 years). 34 patients of that group have hypertension. The control group consisted of 30 healthy children matched according to age and sex. RESULTS: In children with hypertension we found significantly often occurrence of microalbuminuria (13/34 i 1/38, p<0.001). In 17 patients from the group with hypertension and 17 patients without hypertension we affirm signs of autonomic neuropathy. The values of heart rate variability (HRV) were significantly decreased in the group with hypertension as compared to the control group. A stepwise multiple regression analysis with hypertension as a dependent variable and diabetes duration time, microalbuminuria, HbA1c level, HRV parameters and a presence of autonomous neuropathy as predictors proved that hypertension is associated with higher HbA1c level (b=0.35), the presence of autonomous neuropathy (b=0.28), and lower HF values (b=0.41) (p<0.01). CONCLUSIONS: Hypertension in children with type 1 diabetes mellitus is correlated with the presence of autonomous neuropathy, higher HbA1c level and lowered values of heart rate variability parameters.

Assessment of O-methylated catecholamine levels in plasma and urine for diagnosis of autonomic disorders.

The term 'metanephrines' is used to indicate the two catechol 3-O-methylated metabolites of epinephrine (E) and norepinephrine (NE): metanephrine and normetanephrine (NMN). The corresponding 3-O-methylated metabolite of dopamine is usually referred to as 3-methoxytyramine rather than 3-methoxydopamine and is not generally considered a "metanephrine". O-Methylation occurs outside the sympathetic neuron and neuroeffector junction. Metanephrines are products of the enzyme catechol-O-methyltransferase (COMT). Subsequent conjugation with sulfate or deamination by monoamine oxidase (MAO) followed by reduction to vanilmandelic acid (VMA) facilitates urinary excretion. For the clinician, measurement of normetanephrine provides an index of norepinephrine released during sympathetic nervous system activity, whereas metanephrine concentration provides an indication of adrenal medullary metabolism of epinephrine prior to its discharge into the circulation. Plasma epinephrine concentration is the preferable index of adrenal medullary epinephrine discharge. Pheochromocytomas, with their protean clinical manifestations, may be diagnostic challenges, but assay of metanephrines, especially plasma metanephrine, can be particularly helpful in diagnosis. These COMT metabolites may also help in elucidation of still undiscovered genetic and acquired disorders of catecholamine metabolism.

Cardiovascular autonomic neuropathy is associated with microalbuminuria in older patients with type 2 diabetes.

OBJECTIVE: Cardiovascular autonomic neuropathy is associated with microalbuminuria in young and middle-aged patients with type 2 diabetes. We examined this relationship and the potential mediating role of blood pressure in older patients. RESEARCH DESIGN AND METHODS: At least two of three components of cardiovascular autonomic testing were completed by 132 patients (mean age 70 +/- 5.6 years). Relative rankings on each of the components were averaged to create a summary heart rate variability (HRV) measure. The urine microalbumin-to-creatinine ratio (milligrams albumin/grams creatinine) was calculated. Blood pressure was measured at rest and by 24-h ambulatory recording. RESULTS: Urine microalbumin-to-creatinine ratio was higher in those with lower HRV (mean urine microalbumin-to-creatinine ratio 28, 56, and 191 mg/g from the highest to lowest tertile of HRV; P < 0.0001). Resting and ambulatory blood pressure levels were negatively correlated with HRV and positively correlated with urine microalbumin-to-creatinine ratio. In multivariate analysis adjusting for age, duration of diabetes, HbA(1c), and HDL cholesterol, HRV and blood pressure were both independently associated with urine microalbumin-to-creatinine ratio, with no evidence that either mediates the effect of the other. CONCLUSIONS: Cardiovascular autonomic neuropathy and blood pressure are independently associated with microalbuminuria in older patients with type 2 diabetes.

Urinary cortisol:creatinine ratios in healthy horses and horses with hyperadrenocorticism and non-adrenal disease.

Urinary cortisol and creatinine concentrations, and the cortisol:creatinine ratio were compared between 12 healthy horses (group 1), 13 horses with Cushing's disease (group 2), and eight horses with dysautonomia syndrome (equine grass sickness) (group 3). The mean (sd) urinary cortisol concentrations were 112 (55.7), 250 (357) and 864 (526) nmol/litre in groups 1, 2 and 3, respectively; the mean (sd) urinary creatinine concentrations were 18.9 (7.3), 12.0 (6.7) and 45.2 (26.4) nmol/litre in groups 1, 2 and 3, respectively, and the mean (sd) ratios were 6.1 (2.6), 19.8 (23.8) and 21.3 (14.5) (x 10(-6)) in groups 1, 2 and 3, respectively. The urinary cortisol and creatinine concentrations were significantly greater in group 3 than in groups 1 and 2, but the ratios were not significantly different, although there was a trend (P=0.076) towards higher values in groups 2 and 3. A diagnostic cut-off in the cortisol:creatinine ratio for the confirmation of Cushing's disease of more than 6.9 x 10(-6) was associated with a diagnostic sensitivity and specificity of 92.3 and 75.0 per cent, respectively, when compared with healthy horses. However, when group 3 horses were included, a cut-off of more than 7.4 x 10(-6) was associated with a diagnostic sensitivity and specificity of 84.6 and 54.5 per cent, respectively.

Evaluation of urinalysis as an aid in the diagnosis of equine grass sickness.

To determine whether urinalysis can aid the diagnosis of equine grass sickness, samples of urine from 15 horses with acute grass sickness, eight horses with subacute grass sickness, 17 co-grazing horses and 17 stabled control horses were analysed. The samples from all of the horses with grass sickness had a significantly higher specific gravity, higher protein and creatinine concentrations and a significantly lower pH; the samples from the horses with acute grass sickness also had significantly higher glucose concentrations. These differences may support a diagnosis of grass sickness but they are not pathognomonic for the disease.

[Acute polyradiculoneuritis and dysautonomia: contribution of assaying catecholamines and their methoxylated metabolites]. / Polyradiculonévrites aiguës et dysautonomie: pertinence du dosage des catécholamines et des dérivés méthoxylés.

Guillain-Barré syndrome is an acute demyelinating polyradiculoneuritis usually evolving with rapid, functional recovery. In severely paralysed patients, cranial nerve palsy and autonomic nervous system dysfunctions are common. Lesions of the spinal roots predominate but segmentary demyelination of peripheral nervous system reflects various clinical subtypes. Twelve patients (42,8 p. cent) had clinical dysautonomia. Ten had an increase of urinary methoxylated metabolites. Patients exempt of dysautonomia had normal biological parameters. The elevated level of urinary methoxylated metabolites is statistically correlated to clinical dysautonomia and can be used as a biological marker to monitoring demyelinating polyradiculoneuritis.

Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is associated with urinary albumin excretion rate and 24-h ambulatory blood pressure: the Fredericia Study.

The aim of this study was to examine the impact of parental type 2 diabetes on the autonomic nervous system and to determine whether autonomic neuropathy is present and associated with changes in 24-h ambulatory blood pressure (AMBP) and urinary albumin excretion rate (UAER) in nondiabetic subjects with parental type 2 diabetes. We examined 223 nondiabetic offspring of type 2 diabetic subjects and a control group of 258 offspring of nondiabetic subjects. The autonomic nervous system was assessed by three cardiovascular reflex tests, 24-h AMBP was measured with an oscillometric recorder (90207; Spacelabs, Redmond, WA), and UAER was determined through three overnight urine samples. The subjects with parental type 2 diabetes had significantly lower heart rate variation in all three bedside tests (P < 0.01) than subjects without parental diabetes. The prevalence of autonomic neuropathy in the nondiabetic offspring with parental type 2 diabetes (6.7%) was significantly (P < 0.01) higher compared with the control group (1.6%). Autonomic neuropathy was associated with a higher fasting insulin level (P < 0.05), higher UAER (P < 0.001), higher 24-h mean AMBP (P < 0.01), and reduced diurnal blood pressure variation (P < 0.001) after adjustment for age, sex, and BMI. In conclusion, parental type 2 diabetes was found to be associated with alterations in the autonomic nervous system in nondiabetic subjects. The presence of autonomic neuropathy in subjects with parental type 2 diabetes was associated with higher UAER, fasting insulin level, and 24-h AMBP and a reduced diurnal blood pressure variation. This study indicates that parental type 2 diabetes has an impact on the cardiac autonomic function in nondiabetic subjects.

[Autonomic neuropathy in patients with type 2 diabetes and microalbuminuria]. / Autonomní neuropatie u nemocných s diabetem 2. typu a mikroalbuminurií.

BACKGROUND: Microalbuminuria (MAU) represents in patients with type 2 diabetes a risk factor for total and cardiovascular mortality and morbidity, whose principal pathogenic mechanism is the development of atherosclerosis. Other factors may also participate, e.g., cardiovascular vegetative neuropathy, which is supposed to be an independent risk factor. The aim of the study was the analysis of the cardiovascular autonomic regulations in patients with type 2 diabetes and microalbuminuria. METHODS AND RESULTS: 16 patients with type 2 diabetes and microalbuminuria and 23 healthy controls were included in the study. Heart rate variability was tested (during short-term recording at rest, deep breathing, orthostasis and Valsalva manoeuvre) and spectral analysis of telemetric records of heart rate in three positions (lying--standing--lying) was employed. In the group of patients with type 2 diabetes and MAU, in comparison with patients without MAU and controls, significant differences in heart rate variability during deep breathing were found. In comparison to controls, differences were found also during the Valsalve manoeuvre. In parameters of reaction of the heart rate to orthostasis, both groups of diabetic patients differed from controls. When comparing patients with MAU and controls significant differences were also found in spectral analysis of the heart rate variability, namely in total spectral power and the power of the low frequency band in both recumbent positions. In the same parameters, significant differences were found also between patients with and without MAU. The later were not different from the controls. CONCLUSIONS: The presented results indicate the existence of a significant impairment of the autonomic nervous system in patients with type 2 diabetes and microalbuminuria. This fact may contribute to the higher cardiovascular risk in this group of diabetic patients.

Cyclic guanosylmonophosphate urinary excretion in parasympathicomimetic or parasympatholytic syndromes induced by reserpine or diphemanil-methylsulfate.

Parasympathetic hyperactivity is found in some infants presenting faint episodes and could be responsible of certain Sudden Infant Death Syndrome cases. Therefore it was interesting to look for a noninvasive biochemical indicator of parasympathetic activity. A parasympaticomimetic syndrome associated with muscarinic receptor stimulation, which has been followed during 48 h, was obtained in the awake rat by reserpine injection (6.25 mg/kg at T0 and T24h), and a model of prolonged parasympatholytic syndrome, by administration of diphemanil-methylsulfate (DPMS), a muscarinic receptor inhibitor, in drinking water (mean daily dosis: 150 mg/kg). Significant bradycardia and tachycardia were respectively observed. In the reserpine-treated rats we found significantly increased cyclic guanosylmonophosphate (cGMP) urinary excretion between T24h and T48h, when compared with vehicle-treated controls (+87% in one experiment, +135% in the other, when expressed in pmol/microg creatinine); norepinephrine urinary excretion between T24h and T48h was decreased (-44%); the increase in cGMP urinary excretion was not significantly modified by the NO-synthase inhibitor, L-nitroarginine-methyl-ester. In the DPMS-treated rats, we observed a significantly decreased cGMP (-20%) and increased norepinephrine urinary excretion (+61%). Thus cGMP excretion varied in opposite directions in the reserpine- and DPMS-treated rats. The link between these modifications in cGMP excretion and muscarinic receptor stimulation or blockade has still to be fully demonstrated. Urinary cGMP excretion could be tested as screening parameter in infants at risk of faint episodes associated with bradycardia.

Decreased urinary catecholamines in a cat with dysautonomia.

Feline dysautonomia was diagnosed in a 2-year-old cat with a history of regurgitation, constipation, mydriasis, and dry eyes. The diagnosis of parasympathetic and sympathetic failure was confirmed by abnormal physiologic autonomic function tests and decreased urinary catecholamine measurements. Despite intensive supportive care, the cat failed to improve and was euthanatized 70 days after the onset of illness. Feline dysautonomia is rarely reported in the United States, and the cat had no history of travel to a country where the disease is more prevalent.

Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.

[Urine excretion of PGE2, PGF2 alpha in patients with deficiency-cold syndrome and deficiency-heat syndrome].

The 3 hours' urine excretion of PGE2 and PGF2 alpha in 32 patients and 19 healthy persons were determined by RIA. According to TCM, the patients were divided into two groups: 17 cases of deficiency-cold syndrome and 15 cases of deficiency-heat syndrome. The result showed that in patients with deficiency-cold syndrome, the excretion of urine PGE2 was lower than that of the normal control (P less than 0.05), while the excretion of urine PGF2 alpha higher than that of the normal control (P less than 0.01) and hence the PGE2/PGF2 alpha ratio was much lower (P less than 0.01); in those with deficiency-heat syndrome, the excretion of urine PGE2 was higher (P less than 0.01), the excretion of urine PGF2 alpha had no significant change (P greater than 0.05) from the normal, and the PGE2/PGF2 alpha ratio was higher (P less than 0.01). The above result indicates a close relationship between prostaglandins and the cold and heat nature of syndromes in TCM. In connection with our previous studies that showed decreased functioning of the sympathetic-adrenomedullary system and/or increased functioning of the parasympathetic nervous system with diminished catecholamines and reduced cAMP/cGMP ratio in deficiency-cold syndrome while increased functioning of the sympathetic-adrenomedullary system with augmented catecholamines and cAMP in deficiency-heat syndrome, the change of prostaglandins level can be considered as an intermediate link in the pathogenesis of syndromes different in cold and heat nature.

Abnormal diurnal urinary sodium and water excretion in diabetic autonomic neuropathy.

1. Diurnal patterns of urine output and sodium and potassium excretion were studied in 10 diabetic patients with and 10 without autonomic neuropathy, and in 10 normal subjects. 2. The diurnal patterns of excretion in the diabetic patients with autonomic neuropathy differed significantly from the two other groups, as a smaller proportion of the 24 h output of urine, sodium and potassium was excreted during the day and a larger proportion was excreted at night. 3. Similar changes were noted in the diurnal patterns of urinary kallikrein excretion in diabetic patients with autonomic neuropathy, and urinary kallikrein output correlated significantly with urine volume but not with urinary sodium excretion. 4. The diurnal patterns of excretion of urinary prostaglandin E2 and 6-keto-PGF1 alpha were not significantly different in diabetic patients with autonomic neuropathy. 5. Nocturia was a common complaint in this group, and the number of nocturnal voidings correlated with night urine volume. There was no evidence of premature bladder emptying. 6. The changes observed in the day/night urine output and sodium excretion could not be explained by glycosuria, insulin regimens, impaired renal function or abnormal diurnal prostaglandin excretion; their possible relevance to the diurnal changes of urinary kallikrein excretion is discussed.

The relationship between autonomic neuropathy and urinary sodium and albumin excretion in insulin-treated diabetics.

There is evidence to suggest that renal function may alter in the presence of autonomic neuropathy. Albumin excretion rate (AER) and sodium excretion rate (NaER) in timed daytime (erect) and night-time (supine) urine collections were assessed in 20 insulin-treated diabetics with and in 20 without established autonomic neuropathy, matched for age, sex, duration of diabetes, diabetic control, and systolic blood pressure. All patients were free of proteinuria on albustix testing and had normal serum levels of urea and creatinine. AER based on daytime and pooled 24-hour collections was higher, but not significantly so, in the group with autonomic neuropathy. The nocturnal AER on the other hand was significantly elevated in the group with autonomic neuropathy (p less than 0.02) as was the nocturnal urine volume (p less than 0.01) and sodium excretion rate (p less than 0.05). The corrected nocturnal albumin/creatinine ratio was likewise greater in this group (p less than 0.02). These findings suggest that autonomic neuropathy can independently affect renal function and that nocturnal renal haemodynamics and glomerulotubular balance may be deranged in insulin-treated diabetics with autonomic neuropathy.

The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure.

Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst. Desmopressin may be a useful alternative to, or may supplement, other forms of treatment in some patients with autonomic failure.

Prostacyclin biosynthesis and platelet function in autonomic dysfunction.

We measured urinary excretion of the principal metabolite of prostacyclin, PGI-M (2,3-dinor-6-keto-PGF1 alpha) in two patients with Shy-Drager syndrome and three with idiopathic orthostatic hypotension. All patients had a rise in blood pressure (30 +/- 6 mm Hg) after ingestion of 50 mg indomethacin. Urinary excretion of PGI-M was normal and fell 57 +/- 11% after administration of indomethacin. In two subjects, there was no evidence of any circulating inhibitor of platelet aggregation when hypotension was induced by upright posture or ingestion of a meal. Despite the efficacy of indomethacin, these patients with autonomic dysfunction did not show increased production of the vasodilator prostanoid prostacyclin.

Congenital sensory neuropathy with anhydrosis-a case report and investigation of autonomic nervous system abnormalities.

A review of the clinical profile of congenital sensory neuropathy with anhydrosis is presented. It is stressed that major diagnostic criteria of this recessively inherited condition should be limited to insensitivity to pain with normal tactile perception, anhydrosis, recurrent unexplained fever, self-mutilation, mental retardation, hypotonia, histologically normal sweat glands and variable autonomic abnormality. A case conforming to this description is reported and compared with 13 published cases. Special investigations of the autonomic nervous system through measurement of urinary catecholamine metabolites and psychophysiologic variables were conducted on this patient. Based on the analysis of 5 X 24-hour urine, values of metabolites of dopamine and epinephrine were normal. Metabolites of norepinephrine, such as 3-methoxy-4-hydroxy phenylglycol and normetanephrine, however, were significantly low when compared with those of four controls, suggesting decreased peripheral and central norepinephrine activity. Polygraph recording and evaluation of some orienting response components revealed no obvious signs of autonomic perturbation and, specifically, no phasic electrodermal activity. These two findings (biochemical and electrodermal) strongly suggest an autonomic imbalance, specifically component, both central and peripheral. It is suggested that autonomic disorder is an integral part of the syndrome and may be demonstrated by special investigations.