A case of periodic sweating associated with a subarachnoid cyst and multifocal dystonia

Acase of periodic sweating with multifocal dystonia is reported in a 60-year-old woman. At the age of 48 years, she presented with involuntary twisting of the lower face on the right. Six months later she noticed similar movements in the head and right arm. Four years later she began having attacks of generalized sweating over the whole face, anterior region of the trunk and both arms. The attacks occurred hourly each and every day. They lasted for about 10 min and were followed by voluntary urinary voiding. The biochemical and laboratory investigations showed no abnormalities except for the luteinizing hormone and follicle-stimulating hormone values that were below normal. The computerized tomography and magnetic resonance imaging scans revealed a suprasellar cyst. Clonazepam was introduced with partial improvement of the dystonic movements but not of the sweating attacks. The patient refused surgery. Acetazolamide was added and reduced the sweating attacks. We speculate that the periodic sweating may be related to cerebrospinal fluid production and cyst enlargement, hence the ability of acetazoleamide, which reduces cerebrospinal fluid production, to reduce attacks.     

Acute effects of acetazolamide on cerbral blood flow in man

We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i. v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PCO₂- arterial PCO₂, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75% increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the CO₂ reactivities, given as ACBF/ΔPACO₂ in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PACO₂ level. The present dose of the drug caused no change in ventilation, alveolar and arterial PCO₂ or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PCO₂′s. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.     

Enzyme secretion by the isolated rabbit pancreas: Absence of a relation with the Na−K activated ATPase

Summary The isolated rabbit pancreas secretes protein and -amylase at a relatively constant rate during an eight-hour period. Ouabain (10^–5 and 10^–6 M) did not alter enzyme secretion, but inhibited flow (65% and 28% respectively). Acetazolamide (10^–3 M) had no effect on pancreatic enzyme secretion, while flow was inhibited by 25%. Na azide (10^–2 M) failed to affect protein and -amylase secretion. Flow was inhibited by approximately 88%. NaF (10^–2M) increased both protein and -amylase secretion, while flow remained virtually unchanged. Gassing of the bathing fluid with 95% N₂–5% CO₂ reduced protein and -amylase secretion by 57 and 64% respectively, while flow was decreased by 77%. Lowering of the sodium concentration in the bathing fluid by 85% decreased -amylase secretion by 46%. Flow was inhibited by 77%. Return to the standard solution caused initially an increase of -amylase secretion (86%), followed by a decrease. These results strongly suggest that the enzyme secretion of the pancreas is not coupled to the sodium pump, responsible for fluid and electrolyte secretion.     

A microperfusion investigation of bicarbonate secretion by the rat submaxillary gland

Summary Bicarbonate transport in the rat submaxillary main duct has been studied by microperfusion. Bicarbonate was concentrated in the duct lumen against an electrochemical gradient and the equilibrium concentration was estimated to be 56.5 mEq/l±3.1 (S.E.M.,n=11). The secretory mechanism could not be inhibited by 6 mMolar cyanide although such concentrations caused marked inhibition of both net sodium efflux and net potassium influx. Bicarbonate secretion in the main duct was not inhibited by acetazolamide whether applied from the duct lumen or given intravenously. Similarly, the drug was without effect on bicarbonate excretion by the intact gland even when maximum excretory rates had been induced with carbachol. It was concluded that catalytic hydration of carbon dioxide to carbonic acid was not a rate-limiting step in the bicarbonate secretory process. The data did not permit a distinction to be made between a bicarbonate secretory processper se and a process of either H⁺ reabsorption or OH^– secretion.The parasympathomimetic agent, carbachol, when given parenterally was found to increase sharply the net influx of bicarbonate into the microperfused main duct as well as to reduce net sodium efflux and net potassium influx. Previously it had been postulated that final saliva was formed in two stages. First a plasma-like primary secretion was formed at a rate depending on the degree of stimulation, and second, the primary secretion was modified in the gland duct system by reabsorptive and secretory processes whose transport rates were presumed to be independent of the degree of stimulus. It now becomes necessary to postulate that stimulation can act on electrolyte transport at both primary and secondary levels; at present, however, no data are available to show whether appreciable net water influx can ever occur at the secondary level.Preliminary reports of this study have been presented to the Australian Physiological and Pharmacological Society [28, 31].     

Spontaneous improvement in reduced vasodilatory capacity in major cerebral arterial occlusive disease

Reduced vasodilatory capacity resulting from occlusive lesions of the major cerebral arteries may return to normal without surgical revascularisation. We aimed to determine prospectively the frequency and predictors of recovery of impaired haemodynamics as demonstrated by acetazolamide (ACZ) reactivity on single-photon emission computed tomography (SPECT). Vasoreactivity was measured by ¹²³I-IMP SPECT with an ACZ challenge, in 37 medically treated patients with unilateral occlusive disease of the internal carotid or middle cerebral artery at an interval of 1–2 years. Each ACZ challenge test was analysed semiquantitatively by calculating the degree of increase in cerebral blood flow (CBF) asymmetry after ACZ administration (ΔAI). Vasodilatory capacity was abnormal initially in 20 patients (65 %); eight of whom (40 %) exhibited spontaneous normalisation on follow-up. Although the baseline characteristics did not differ significantly between patients with or without increase in reactivity, logistic regression analysis revealed that the initial ΔAI (P < 0.05) and the type of vascular lesion (stenosis or occlusion) (P < 0.05) correlated significantly with a return towards normal of reduced ACZ reactivity. Spontaneous improvement of impaired vasodilatory capacity may not be a rare phenomenon. We found that mild reduction in the initial ACZ reactivity and a stenosis, but not complete occlusion, were independent factors contributing to normalisation of impaired cerebral haemodynamics. Received: 12 October 1998/Accepted: 27 April 1999     

Acetazolamide: A New Treatment for Visual Vertigo

Visual vertigo is a disorder characterised by symptoms of dizziness, vertigo, unsteadiness, disorientation, and general discomfort induced by visual triggers. It is currently treated with vestibular rehabilitation therapy, with no effective pharmacotherapy available for treatment-resistant cases. The objective of this study was to evaluate the efficacy of oral acetazolamide in improving symptoms of visual vertigo. A comparative case series of adult patients clinically diagnosed with visual vertigo was conducted from January 1992 to May 2015. Patients without a full neurologic or otorhinolaryngologic work-up, negative magnetic resonance imaging (MRI), and an organic cause for their symptoms were excluded. The identified patients were then contacted by phone to complete a voluntary symptom survey. Main outcome was the subjective reported percentage in symptom improvement. Secondary outcomes were subjective improvement by symptom triggers. The participants were retrospectively divided into three groups based on their treatment with acetazolamide: currently on acetazolamide, terminated acetazolamide, or never initiated acetazolamide. Fifty-seven patients met the inclusion criteria and were willing to complete the phone survey (19 currently on acetazolamide, 27 terminated acetazolamide, and 11 never initiated therapy). Overall symptomatic improvement was reported by 18 (94.7%) patients currently on acetazolamide, 18 (66.7 %) who terminated acetazolamide, and 5 (45.5%) who never initiated therapy, varying significantly by group (p = 0.0061). Greatest improvement was reported in symptoms triggered by being a passenger in a car. These results show that acetazolamide has a positive association with improvement of symptoms of visual vertigo.     

Budesonide Versus Acetazolamide for Prevention of Acute Mountain Sickness

Background

Inhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide.

Efficacy of Acetazolamide for the Prophylaxis of Acute Mountain Sickness: A Systematic Review,Meta-Analysis and Trial Sequential Analysis of Randomized Clinical Trials

BackgroundAcute mountain sickness (AMS) is a benign and self-limiting syndrome but can progress to life-threatening conditions if leave untreated. This study aimed to assess the efficacy of acetazolamide for the prophylaxis of AMS and disclose potential factors that affect the treatment effect of acetazolamide.Materials and MethodsRandomized controlled trials comparing the use of acetazolamide versus placebo for the prevention of AMS were included. The incidence of AMS was the primary endpoint. Meta-regression analysis was conducted to explore potential factors associated with acetazolamide efficacy. Trial sequential analysis (TSA) was conducted to estimate the statistical power of the available data.ResultsA total of 22 trials were included. Acetazolamide at 125, 250, and 375 mg/ twice daily (bid) significantly reduced incidence of AMS compared to placebo. TAS indicated that the current evidence was adequate confirming the efficacy of acetazolamide at 125, 250, and 375 mg/bid in lowering incidence of AMS. There was no evidence of an association between efficacy and dose of acetazolamide, timing at start of acetazolamide treatment, mode of ascent, AMS assessment score, timing of AMS assessment, baseline altitude, and endpoint altitude.ConclusionAcetazolamide is effective prophylaxis for the prevention of AMS in doses of 125, 250, and 375 mg/bid. Future investigations should focus on personal characteristics, disclosing the correlation between acetazolamide efficacy and body mass, height, degree of prior acclimatization, individual inborn susceptibility, and history of AMS.     

Pharmacological interventions for preventing acute mountain sickness: a network meta-analysis and trial sequential analysis of randomized clinical trials

Background: Individuals ascending to high altitude are at a risk of getting acute mountain sickness (AMS). The present study is a network meta-analysis comparing all the interventions available to prevent AMS.

Methods: Electronic databases were searched for randomized clinical trials evaluating the use of drugs to prevent AMS. Incidence of AMS was the primary outcome and incidence of severe AMS, paraesthesia (as side effect of acetazolamide use), headache and severe headache, and oxygen saturation were the secondary outcomes. Odds ratio [95% confidence interval] was the effect estimate for categorical outcomes and weighted mean difference for oxygen saturation. Random effects model was used to derive the direct and mixed treatment comparison pooled estimates. Trial sequential analysis and grading of the evidence for key comparisons were carried out.

Results: A total of 24 studies were included. Acetazolamide at 125, 250 and 375?mg twice daily, dexamethasone and ibuprofen had statistically significant lower incidence of AMS compared to placebo. All the above agents except ibuprofen were also observed to significantly reduce the incidence of severe AMS. Acetazolamide alone or in combination with Ginkgo biloba were associated with lower incidence of headache, but higher risk of paraesthesia. Acetazolamide at 125?mg and 375?mg twice daily significantly reduce the incidence of severe headache as like ibuprofen. Trial sequential analysis indicates that the current evidence is adequate for the incidence of AMS only for acetazolamide 125 and 250?mg twice daily. Similarly, the strength of evidence for acetazolamide 125 and 250?mg twice daily was moderate while it was either low or very low for all other comparisons.

Conclusions: Acetazolamide at 125, 250 and 375?mg twice daily, ibuprofen and dexamethasone significantly reduce the incidence of AMS of which adequate evidence exists only for acetazolamide 125 and 250?mg twice daily therapy. Acetazolamide 125?mg twice daily could be the best in the pool considering the presence of enough evidence for preventing AMS and associated with lower incidence of paraesthesia.

• Key messages

• Acetazolamide 125, 250 and 375?mg twice daily, dexamethasone and ibuprofen reduce the incidence of AMS in high altitudes.

• Adequate evidence exists supporting the use of acetazolamide 125?mg and 250?mg twice daily for preventing AMS of which acetazolamide 125?mg twice daily could be the best.

     

Lack of gender difference in acetazolamide-induced cerebral vasomotor reactivity in patients suffering from type-1 diabetes mellitus

The aim of the present work was to investigate the impact of gender on resting cerebral blood flow velocity and cerebrovascular reserve capacity among diabetic patients. Middle cerebral artery mean blood flow velocity (MCAV) was measured in 72 patients suffering from type 1 diabetes mellitus at rest and 5, 10, 15 and 20 min after intravenous administration of 1 g acetazolamide. Cerebrovascular reserve was calculated as the maximal percent increase in MCAV after acetazolamide. Resting MCAV and cerebrovascular reserve capacity were compared between males and females. Resting cerebral blood flow velocity was higher in diabetic females than in males (men, 55.0±17.0 cm/s; women, 64.4±12.6 cm/s, p=0.00094). Cerebrovascular reserve capacity was similar in diabetic women and men (men, 44.0%±18.6%; women, 52.6%±32.9%, p=0.17). Comparing MCAV and cerebrovascular reserve capacity among the diabetic subgroups with disease duration ≤10 years and >10 years, we did not detect any differences between women and men. Duration of diabetes was an important factor in determining cerebrovascular reserve capacity in both sexes: long-term diabetic women and men showed lower CRC values than diabetics with ≤10 years, disease duration. Cerebrovascular reserve capacity is similar in diabetic women and men. Taking into consideration that cerebrovascular reserve is normally higher among women, our finding indicates a relatively more serious worsening of cerebral vasodilatory responses in women suffering from type 1 diabetes. Received: 20 May 2000 / Accepted in revised form: July 2001