Autonomic Nervous System Response to Stressors in Newly Diagnosed Patients with Multiple Sclerosis.

Autonomic dysfunction is commonly detected in patients with multiple sclerosis (MS). However, data evaluating autonomic nervous system function in early MS are limited. Present study investigates response to two different stressors in newly diagnosed MS patients, looking for the signs of autonomic dysfunction at the beginning of the disease. We examined 19 MS patients and 19 age, sex, and body mass index matched healthy controls. MS patients were newly diagnosed, untreated, and with low expanded disability status scale (EDSS) values [median 1.0 (interquartile range 1.0-1.5)]. Two stressors were used to evaluate the response of autonomic nervous system: Stroop word-color interference mental stress test and orthostasis. Plasma levels of epinephrine and norepinephrine, blood pressure (BP), and heart rate variability (HRV) parameters were evaluated. At the end of Stroop test MS patients had lower systolic BP (121 ± 15 vs. 132 ± 17 mmHg, p = 0.044), lower heart rate (79 ± 9 vs. 88 ± 16 1/min, p = 0.041), and lower epinephrine increment (10 ± 22 vs. 30 ± 38 pg/ml; p = 0.049) compared to healthy controls. Norepinephrine response was unaffected in MS, however, with lower norepinephrine levels during the test (p = 0.036). HRV parameters were similar in both groups. No differences in BP, heart rate, catecholamines, and HRV parameters between groups during orthostatic testing were found. We found slightly diminished sympathetic response to mental stress test, but unchanged response to orthostasis, in newly diagnosed untreated MS patients. The results suggest that autonomic dysfunction in MS is connected with more developed disease.

Adrenomedullin and galanin responses to orthostasis in older persons.

BACKGROUND: Neuroendocrine responses to orthostasis may be critical in the maintenance of mean arterial pressure in healthy individuals. A greater reduction in orthostatic tolerance with age may relate to modulation of hormonal responses such as adrenomedullin and galanin. Thus, we investigated (i) whether adrenomedullin and galanin concentrations increase during orthostatic challenge in older subjects, (ii) whether adrenomedullin and galanin concentrations are higher in older females compared with older males when seated and during orthostatic challenge, and (iii) whether postural changes in plasma concentrations of galanin are correlated with levels of adrenomedullin in either older females or males. MATERIALS AND METHODS: Subjects (n = 18; 12 ♀; 55-80 years old) performed a sit-to-stand test in a 25°C sensory-minimised environment, with blood samples collected after 4 min of being seated and then when standing. Plasma adrenomedullin and galanin concentrations were determined. RESULTS: Baseline plasma concentration of adrenomedullin (5·35 ± 0·74 (n = 12, females) vs. 7·40 ± 1·06 pg/mL (n = 5, males)) and galanin (64·07 ± 9·05 vs. 98·99 ± 16·90 pg/mL, respectively) did not significantly differ between genders. Furthermore, plasma adrenomedullin and galanin concentrations were not significantly affected by adoption of the upright posture in either gender and were not correlated in females or males. CONCLUSIONS: Adrenomedullin and galanin concentrations were similar between genders and did not change following adoption of the standing posture. To further clarify the roles, these hormones play in orthostatic intolerance, adrenomedullin and galanin concentrations should be assessed in participants who show presyncopal symptoms during an orthostatic challenge.

Unexplained spikes in lamotrigine serum concentration: nonlinear elimination?

OBJECTIVES: The objective of this study was to evaluate possible nonlinear lamotrigine (LTG) pharmacokinetics at elevated concentration. LTG is reported to have linear kinetics, so that elimination rate is linearly proportional to blood concentration and a change in dose is accompanied by a proportionate change in serum concentration. We encountered patients in whom LTG serum concentration increased dramatically in response to minor or no change in LTG dose. We studied this phenomenon in patients with LTG toxicity in one clinic. MATERIALS AND METHODS: Using electronic medical records from 1997 to 2014, we identified patients who developed clinical LTG toxicity with LTG serum concentrations >20 mg/l, after tolerating lamotrigine at lower serum concentrations. We reviewed LTG dose change and other changes that preceded the episode of toxicity. RESULTS: Twenty-two patients had at least one episode of LTG toxicity with levels higher than 20 mg/l (of 922 patients with available levels). The peak serum concentration varied from 21.1 to 40.3 mg/l (mean 28.7). The increase in level was explained in three patients (post-delivery in one, addition of valproate in two). In the 18 others, the increase was not explained or it was disproportionate to an increase in LTG dose. CONCLUSIONS: Spikes in LTG levels and associated clinical toxicity may occur unexpectedly, suggesting that elimination kinetics may be nonlinear in some individuals at serum concentrations in the upper range. Measurement and close monitoring of LTG levels is warranted for new symptoms that could be consistent with lamotrigine toxicity, particularly when the baseline serum concentration has been >10 mg/l.

Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading.

Measurement of the aldosterone to active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but several sampling conditions impact on the AARR. We aimed to evaluate the reproducibility and the influence of orthostasis and salt loading on the AARR. The Graz Endocrine Causes of Hypertension (GECOH) study is a diagnostic accuracy study among hypertensive patients at a tertiary care centre in Graz, Austria. With a median interval of 4 weeks we determined the AARR under standardized sampling conditions twice in the sitting position, after 1h in the supine position, and after a salt infusion test (SIT). We identified 9 patients with PA and 151 patients with essential hypertension (EH). The Pearson correlation coefficient between both AARR measurements in the sitting position was 0.79 (p<0.001). In EH, recumbency was associated with a significant decrease of aldosterone and, to a lesser extent, of renin, thus lowering the AARR as compared to the sitting position (p<0.001 for all). In PA, recumbency had only minor effects, but it increased the rate of false negative AARR. SIT suppressed the AARR and its components in EH, whereas in PA only renin was slightly decreased. AARR has a good intra-individual reproducibility and decreases during recumbency. These results suggest that a single AARR determination in the sitting position is a reliable screening tool for PA.

The role of thyroid and parathyroid metabolism disorders in the etiology of sudden onset dizziness.

BACKGROUND: The aim of this study was to evaluate thyroid and parathyroid functions as a cause of sudden onset dizziness (SOD) in patients who were admitted to the Emergency Department (ED). MATERIAL AND METHODS: This study was conducted prospectively in 100 patients with sudden onset dizziness (SOD) admitted to the ED. Neurologic, ear-nose-throat, detailed neck examinations, serum calcium levels, thyroid function tests (TFT), and parathormone and thyroid ultrasounds were performed on all patients in our study. RESULTS: Thirty-seven (37%) females and 63 (63%) males were included in this study. Four patients (4%) had elevated serum TSH levels, 6 (6%) had decreased serum fT3 levels, 10 (10%) had decreased serum fT4 levels, 2 (2%) had elevated serum fT4 levels, and 2 (2%) had elevated serum parathormone levels. In 4 (4%) patients, the serum calcium levels were lower than normal, and 2 (50%) of these patients had symptomatic hypocalcemia. Thyroid ultrasound examinations showed multinodular goiter in 28 (28%) patients, 2 (2%) patients had thyroiditis, 12 (12%) had an isolated unilateral nodule, and 58 (58%) had normal thyroid tissues. CONCLUSIONS: We suggest that detailed neck examination, TFT, and thyroid ultrasound examination should be considered in the diagnostic algorithms of SOD to provide rapid diagnosis and proper treatment for a patient in the ED.

Worsening of Dizziness Impairment Is Associated with Bone Marrow Kinase on Chromosome X Level in Patients after Mild Traumatic Brain Injury.

Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score [GCS] between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.

Biomarkers of Oxidative Stress and Endogenous Antioxidants for Patients with Chronic Subjective Dizziness.

As a neurotologic disorder of persistent non-vertiginous dizziness, chronic subjective dizziness (CSD) arises unsteadily by psychological and physiological imbalance. The CSD is hypersensitivity reaction due to exposure to complex motions visual stimuli. However, the pathophysiological features and mechanism of the CSD still remains unclearly. The present study was purposed to establish possible endogenous contributors of the CSD using serum samples from patients with the CSD. A total 199 participants were gathered and divided into two groups; healthy (n = 152, male for 61, and female for 91) and CSD (n = 47, male for 5, female for 42), respectively. Oxidative stress parameters such as, hydrogen peroxide and reactive substances were significantly elevated (p < 0.01 or p < 0.001), whereas endogenous antioxidant components including total glutathione contents, and activities of catalase and superoxide dismutase were significantly deteriorated in the CSD group (p < 0.01 or p < 0.001) as comparing to the healthy group, respectively. Serum levels of tumor necrosis factor -α and interferon-γ were significantly increased in the CSD participants (p < 0.001). Additionally, emotional stress related hormones including cortisol, adrenaline, and serotonin were abnormally observed in the serum levels of the CSD group (p < 0.01 or p < 0.001). Our results confirmed that oxidative stress and antioxidants are a critical contributor of pathophysiology of the CSD, and that is first explored to establish features of redox system in the CSD subjects compared to a healthy population.

Circulating endocannabinoid concentrations during orthostatic stress.

BACKGROUND: In animals, the endocannabinoid system is activated during hemodynamic insults and restrains blood pressure in part through sympathetic inhibition. MATERIALS AND METHODS: We tested the hypothesis that hemodynamic stress elicited by head-up tilt testing increases systemic endocannabinoid concentrations in humans and that excessive endocannabinoid availability predisposes to presyncope. RESULTS: With head-up tilt, 2-arachidonoylglycerol increased, whereas anandamide remained unchanged. CONCLUSIONS: In contrast to our expectations, anandamide plasma concentration at rest was directly correlated with orthostatic tolerance, rather than intolerance.

Value of copeptin and the S-100b protein assay in ruling out the diagnosis of stroke-induced dizziness pattern in emergency departments.

BACKGROUND: Dizziness is a frequent reason for visiting emergency departments (EDs). Differentiating stroke from other causes is challenging for physicians. The role of biomarkers has been poorly assessed. We evaluated whether copeptin and S100b protein (PS100b) assessment, alone or in combination, could rule out stroke in patients visiting EDs for dizziness. METHODS: We included patients 18 years of age or older, visiting the adult ED of a French university hospital for a new episode of dizziness evolving for less than 72 h. All patients underwent standardized physical examination (HINT [Head Impulse test, Nystagmus, test of skew deviation] maneuvers), copeptin and S-100b protein (PS100) measurement and injected brain imaging. Stroke diagnosis involved diffusion-weighted magnetic resonance imaging or, if not available, neurological examination and contrast brain CT scan compatible with the diagnosis. RESULTS: Of the 135 patients participating in the study, 13 (10%) had stroke. The sensitivity, specificity and positive and negative predictive values of copeptin/PS100 combination were 100% (95%CI, 77-100%), 48% (40-57%), 14% (11-27%) and 100% (94-100%), respectively. Values for copeptin alone were 77% (CI95% 0.50-0.91), 50% (CI95% 0.49-0.58), 14% (CI95% 0.08-0.24), 93% (CI95% 0.87-0.98), and for PS100 alone were 54% (CI95% 0.29-0.77), 97% (CI95% 0.92-0.99), 64% (CI95% 0.35-0.84), 95% (CI95% 0.90-0.98). CONCLUSIONS: Absence of copeptin and PS100 elevation seems to ruling out the diagnosis of stroke in patients visiting the ED for a new episode of dizziness. These results need to be confirmed in a large-scale study.

Ménière's disease with unremitting floating sensation is associated with canal paresis, gravity-sensitive dysfunction, mental illness, and bilaterality.

OBJECTIVE: The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease. METHODS: We managed 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to April 2018. Five hundred and twenty-two patients were diagnosed with Ménière's disease (522/1520; 34.3%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. Among the patients with Ménière's disease there were 102 with intractable rotatory vertigo attacks for more than 3-6 months (102/522; 19.5%), including 20 bilateral cases (20/102; 19.6%), and 88 with intractable unremitting floating sensation rather than rotatory vertigo attacks for more than 3-6 months (88/522; 16.9%), including 28 bilateral cases (28/88; 31.8%). Sixty out of 88 cases with intractable unremitting floating sensation were unilateral and were enrolled for hospitalization to undergo neuro-otological examinations including pure-tone audiometry (PTA), the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV) test, glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Data are presented as positive (+) ratios of the number of patients with examination and questionnaire data outside of the normal range. RESULTS: The ratios (+) were as follows: C-test=33.3% (20/60), cVEMP=25.0% (15/60), SVV=50.0% (30/60), G-test=55.0% (33/60), ECoG=63.3% (38/60), ieMRI=86.7% (52/60), ADH=35.0% (21/60), BAP=11.7% (7/60), and SDS=40.0% (24/60). Multivariate regression analysis revealed that the periods of persistent dizziness were significantly longer in unilateral Ménière's patients with C-test(+), SVV(+), and SDS(+) compared with those with negative findings. Additionally, the periods in bilateral cases were significantly longer than those in unilateral ones. CONCLUSIONS: Although approximately 70% of patients with Ménière's disease are usually treatable through the appropriate conservative medical therapy, the presence of canal paresis, gravity-sensitive dysfunction, neurosis/depression, and bilaterality may make the persistent dizziness intractable and may thus require additional treatments.

You're The Flight Surgeon.

Beauvais A, Tate J, Kluesner JK. You're the flight surgeon: hypoglycemia. Aerosp Med Hum Perform. 2019; 90(9):826-829.

Clinical and laboratory factors related to acute isolated vertigo or dizziness and cerebral infarction.

OBJECTIVE: To clarify the relationship of clinical factors with isolated vertigo or dizziness of cerebrovascular origin. METHODS: Clinical data of patients admitted in East Hospital from Jan. 2015 to Apr. 2016, whose complaint were acute vertigo or dizziness were retrospectively collected. All patients arrived at the emergency department within 24 hr of symptom onset, had no acute ischemic lesion first CT and NIHSS score of 0. Patients were divided into cerebral infarction group and noncerebral infarction group according to subsequent cerebral imaging results and clinical and laboratory factors related to cerebral infarction were analyzed. RESULT: 51.6% of patients were female (n = 141). 46 patients (16.8%) were diagnosed with acute cerebral infarction. Baseline demographic data of the two groups was not significantly different. Univariate analysis found that history of smoking (p = 0.009), headache (p = 0.028), unsteadiness (p = 0.009), neuron specific enolase (p = 0.001), and vertebral artery abnormalities found on imaging (p = 0.009) were the significant difference between two groups. Increased neuron specific enolase (p = 0.005) and an abnormal vertebral artery (p = 0.044) were significant on multivariate analysis. CONCLUSIONS: 16.8% of acute isolated vertigo or dizziness presentations were diagnosed with acute cerebral infarction. Increased serum neuron specific enolase and vertebral artery abnormalities were the strongest indicators of acute cerebral infarction.

Hyperventilation before resistance exercise: cerebral hemodynamics and orthostasis.

UNLABELLED: Hyperventilation performed by athletes during preparation for resistance exercise might contribute to reports of postexercise orthostatic instability. PURPOSE: To test the hypothesis that post-resistance exercise orthostatic instability is associated with exaggerated reductions of cerebral blood-flow velocity after hyperventilation. METHODS: We recorded the ECG, end-tidal CO2, beat-by-beat finger arterial pressure, and cerebral blood-flow velocity in 10 healthy subjects. Subjects performed 10 repetitions of recumbent leg press using resistance equivalent to 80% of their six-repetition maximum during three separate trials (randomized): 1) no prior hyperventilation (NOHV); 2) after hyperventilation to an end-tidal CO2 of 3% (HV3%); and 3) after hyperventilation to an end-tidal CO2 of 2% (HV2%). After exercise, subjects stood upright for 10 s and rated symptoms of lightheadedness on a scale of 1 (none) to 5 (faint). RESULTS: Mean cerebral blood-flow velocity (CBFV(MEAN)) increased by 12% during exercise after NOHV and decreased by 14 and 25% during exercise after HV3% and HV2% (all P < 0.0001). During standing, mean arterial pressure (MAP) decreased by 96 mm Hg and CBFV(MEAN) decreased by 41 cm.s(-1) (pooled across conditions; all P < 0.0001). Absolute reductions of CBFV(MEAN) during standing were greater after HV2% compared with both NOHV and HV3% (P = 0.003). Ratings of perceived lightheadedness during standing increased with prior hyperventilation (P = 0.02) and correlated to the magnitude of reductions in MAP (r = 0.51; P = 0.003) and CBFV(MEAN) (r = 0.37; P = 0.04). CONCLUSIONS: Hyperventilation before lower-body resistance exercise exacerbates CBFV(MEAN) reductions during standing. Increased symptoms of orthostatic instability are associated with the magnitude of reductions in both MAP and CBFV(MEAN).

From dizziness to severe ataxia and dysarthria: New cases of anti-Ca/ARHGAP26 autoantibody-associated cerebellar ataxia suggest a broad clinical spectrum.

In 2010, a novel anti-neuronal autoantibody, termed anti-Ca, was described in a patient with subacute cerebellar ataxia, and Rho GTPase-activating protein 26 (ARHGAP26) was identified as the target antigen. Recently, three additional cases of anti-Ca-positive cerebellar ataxia have been published. In addition to ataxia, cognitive decline and depression have been observed in some patients. Here, we report two new cases of anti-Ca-associated autoimmune cerebellar ataxia. Patient 1 presented with dizziness and acute yet mild limb and gait ataxia. Symptoms stabilized with long-term oral corticosteroid therapy but transiently worsened when steroids were tapered. Interestingly, both initial occurrence and worsening of the patient's neurological symptoms after steroid withdrawal were accompanied by spontaneous cutaneous hematomas. Patient 2 initially presented with an increased startle response and myoclonic jerks, and subsequently developed severe limb and gait ataxia, dysarthria, oculomotor disturbances, head and voice tremor, dysphagia, cognitive symptoms and depression. Steroid treatment was started five years after disease onset. The symptoms then responded only poorly to corticosteroids. At most recent follow-up, 19 years after disease onset, the patient was wheelchair-bound. These cases extend the clinical spectrum associated with anti-ARHGAP26 autoimmunity and suggest that early treatment may be important in patients with this rare syndrome.

Circulatory galanin levels increase severalfold with intense orthostatic challenge in healthy humans.

The purpose of this study was to test the hypothesis that plasma galanin concentration (pGal) is regularly increased in healthy humans with extensive orthostatic stress. Twenty-six test persons (14 men, 12 women) were brought to an orthostatic end point via a progressive cardiovascular stress (PCS) protocol consisting of 70 degrees head-up tilt plus increasing levels of lower body negative pressure until either hemodynamically defined presyncope or other signs of orthostatic intolerance occurred (nausea, clammy skin, excessive sweating, pallor of the skin). We further tested for possible gender, gravitational, and muscular training influences on plasma pGal responses: PCS was applied before and after 3 wk of daily vertical acceleration exposure training on a Human Powered Centrifuge. Test persons were randomly assigned to active (with bicycle work) or passive (without work) groups (seven men, six women in each group). Resting pGal was 26+/-3 pg/ml in men and 39+/-15 pg/ml in women (not significant); women had higher galanin responses (4.9-fold increase) than men (3.5-fold, P=0.017) to PCS exposure. Overall, PCS increased pGal to 186+/-5 pg/ml (P=0.0003), without significant differences between presyncope vs. orthostatic intolerance, pre- vs. postcentrifuge, or active vs. passive gravitational training. Increases in pGal were poorly related to synchronous elevations in plasma vasopressin. We conclude that galanin is regularly increased in healthy humans under conditions of presyncopal orthostatic stress, the response being independent of gravity training but larger in women than in men.

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope.

OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF). PATIENTS AND METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation. RESULTS: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients. CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

Venous hypertension induces increased platelet reactivity and accumulation in patients with chronic venous insufficiency.

The objective of this study was to determine whether there are changes in platelet activation and rheology in patients with chronic venous insufficiency (CVI) and what their impact is on this disease. Anticoagulated peripheral venous blood collected from 21 patients with CVI and 13 normal control subjects in different bodily positions was incubated either with 0.5 mumol/L adenosine diphosphate (ADP) or without agonist and analyzed by whole blood flow cytometry. Soluble P-selectin was analyzed in obtained sera by enzyme-linked immunosorbent assay. Platelet count was determined by a whole blood analyzer. Circulating platelets were more reactive to stimulation with 0.5 mumol/L ADP in patients with CVI compared with control subjects. There was no statistically significant change in platelet activation without ADP and the level of soluble P-selectin as a function of posture. Under simulated venous hypertension, platelet accumulation was observed in patients with CVI. Patients with CVI had increased platelet reactivity and accumulation during orthostasis, suggesting this might be a contributory factor to CVI pathogenesis.

Postural hypotension and postural dizziness in patients with non-insulin-dependent diabetes.

BACKGROUND: Postural hypotension with a decline of 20 mm Hg or more in systolic blood pressure on standing is considered a potentially dangerous hypotensive response. Postural dizziness is often strongly associated with postural hypotension. However, there is conflicting evidence, and previous studies have been confined to the elderly, not specifically to patients with diabetes. Thus, we evaluated the association between postural hypotension and postural dizziness, and determined the factors most likely related to postural hypotension in patients with diabetes. METHODS: The subjects were 204 consecutive noninsulin-dependent patients with diabetes and 408 age- and sex-matched control subjects. Postural hypotension was defined as a decline of 20 mm Hg or more in systolic blood pressure 1 minute after standing. Postural dizziness was any feelings of dizziness, lightheadedness, or faintness that occurred while standing during the examination. RESULTS: The prevalence of postural hypotension and postural dizziness in patients with diabetes was higher than in control subjects. Those patients with both diabetes and postural hypotension were older and had higher supine systolic blood pressures and higher plasma glycosylated hemoglobin and fasting glucose levels. They had higher prevalence of postural dizziness, hypertension, and cerebrovascular disease, and lower standing systolic blood pressures than those without postural hypotension. They also were more often being treated with antihypertensive agents. Only 32.8% of patients with diabetes with postural hypotension suffered from postural dizziness. Postural dizziness, hypertension, cerebrovascular disease, and plasma glycosylated hemoglobin levels were independently associated with postural hypotension in patients with diabetes. CONCLUSIONS: Postural dizziness, glycemic control, hypertension, and cerebrovascular disease were important determinants of postural hypotension in patients with diabetes. Postural hypotension was associated with postural dizziness, but it cannot be determined clinically just from the presence of postural dizziness because the sensitivity for diagnosis of postural hypotension is low.

Neurohormonal behavior during prolonged orthostatic stress in normotensive subjects.

Prolonged orthostatic stress induces major changes in hemodynamic and autonomic nervous system function. The neurohormonal response to acute and prolonged orthostatic stress that may trigger neurocardiogenic syncope is not clear. The goal of this study was to assess neurohormonal changes during acute and prolonged orthostatic stress. In fifteen normotensive subjects without medication blood was sampled at supine rest (S), during early passive orthostatic stress (after first 10 min.) (T1) and after prolonged (>40 min.) orthostatic stress (T2). We measured atrial and brain natriuretic peptides (ANP and BNP) and catecholamines [norepinephrine (NOR), epinephrine (EPI) and dopamine (DOP)]. ANP was 7.0 +/- 4.3 pmol/l during S, 7.3 +/- 5.1 during T1 and 4.6 +/- 2.8 during T2 (NS and p < 0.05). BNP was 1.9 +/- 1.6 pmol/l during S, 1.7 +/- 1.5 during T1 and 1.4 +/- 1.3 during T2 (p < 0.05 and p < 0.05). NOR was 172 +/- 92 pg/ml during S, 378 +/-_216 during T1 and 402 +/- 183 during T2 (p < 0.01 and NS). EPI was 10.4 +/- 3.8 pg/ml during S, 22.2 +/- 9.3 during T1 and 44.4 +/- 26.0 during T2 (p < 0.01 and p < 0.01). DOP was 7.8 +/- 4.8 pg/ml, 7.6 +/- 2.1 during T1 and 7.0 +/- 2.3 during T2 (NS and NS), Neurohormonal responses to orthostatic stress varied. Natriuretic peptides (ANP and BNP) decreased with prolonged orthostatic stress, probably due to the progressive hypovolemia it induced. Dopamine levels did not change, whereas norepinephrine and epinephrine showed a considerable rise following acute orthostatic stress, with epinephrine rising still further with prolonged orthostatic stress. Neurohormonal responses to prolonged orthostatic stress could help to clarify the pathophysiology of neurocardiogenic syncope.