Administration Of Acetazolamide Research Articles

Effects of acetazolamide on intracranial pressure and brain tissue oxygenation on patients with acute brain injury: A pilot physiological study.

The effect of acetazolamide on regional brain tissue oxygenation in patients with acute brain injury (ABI) is unknown. We studied adult patients with ABI who received acetazolamide as per the treating physician's decision and had ICP and brain oxygen pressure (PbtO2) monitoring. Baseline measurements of ICP, cerebral perfusion pressure (CPP), and PbtO2 were taken before administering acetazolamide; subsequent measurements were recorded every 5 min for a total of 20 min. Mean cerebral blood velocities (FVm) and pulsatility index (PI) were measured using transcranial color-coded duplex (TCCD) sonography at baseline and after 20 min. Fourteen patients with subarachnoid hemorrhage (n = 6), traumatic brain injury (n = 7), and intracranial hemorrhage (n = 1) were included. Following administration of acetazolamide, ICP showed a significant increase within 20 min (p < 0.001), with no significant change in CPP (p = 0.08). PbtO2 demonstrated a significant increase (p < 0.001), with a noticeable change observed at 10 min after acetazolamide administration (15 [14-17] vs. 28 [26-30] mmHg). Additionally, FVm exhibited a significant increase (p < 0.001), and PI showed a reduction (p < 0.001). Administration of acetazolamide in ABI patients resulted in a significant increase in brain oxygenation, associated with a rise in ICP and FVm, suggesting increased cerebral volume and vasodilation.

Cerebral hemodynamics and oxygen metabolism in patients with milder and severe forms of sickle cell disease and thalassemia.

Silent cerebral infarcts (SCIs) are present in patients with sickle cell disease (SCD) and thalassemia, but the pathophysiology of SCIs is not fully understood. Previous studies mainly focused on cerebral hemodynamics and oxygen metabolism in patients with severe SCD (HbSS/HbSβ°) but not in milder forms of SCD (HbSC/HbSβ+) and thalassemia despite the high prevalence of SCIs in these patients. In this work, we studied the cerebral hemodynamics and oxygen metabolism, and SCI lesion load in 75 severe and 26 mild adult SCD patients, 18 thalassemia patients (as anemic comparison group), and 30 healthy controls before and after a vasodilatory challenge with acetazolamide. Cerebral blood flow was significantly higher in patients with severe SCD and thalassemia compared to patients with mild SCD and controls (p < 0.05). Conversely, oxygen extraction fraction and cerebral metabolic rate of oxygen (CMRO2) were significantly lower in patients with severe SCD and thalassemia compared to other groups (p < 0.01). In contrast, no difference in SCI volumes was found between mild and severe SCD and thalassemia patients. After acetazolamide administration, oxygen delivery increased less in severe SCD and thalassemia patients compared to other groups (p < 0.01) and CMRO2 decreased only in severe SCD patients (p < 0.01). Given the reduced CMRO2 values in severe SCD and thalassemia patients, we conclude that reduced cerebral oxygen consumption in these patient groups is mostly related to anemia. Our data suggest that the pathophysiology of SCIs in patients with milder forms of SCD might be more related to prior episodes of anemia or other sickle cell-related factors.

Abstract 331: MR Steal Phenomenon Corresponds to Cerebral Angiogram Circulation Time

Background Cerebrovascular reserve (CVR) is crucial for assessing hemodynamic impairment in patients with cerebrovascular steno‐occlusive disease. While catheter cerebral angiography is the gold‐standard for evaluating CVR and collateral circulation, acetazolamide‐challenged arterial spin labeling perfusion MRI (AC‐ASL) has emerged as a non‐invasive alternative, but its effectiveness in reflecting neuroangiographic parameters is not fully understood. Methods A retrospective study was conducted on patients who underwent AC‐ASL from 2014‐2022. Patients were excluded if concurrent angiographic analysis was not performed, or image quality was compromised. The study involved correlating cerebral angiographic metrics like arteriocapillary circulation time (ACCT) and superior sagittal sinus entry (SSSE) with AC‐ASL flow parameters in patients with steno‐occlusive disease. MR acquisitions were obtained prior to acetazolamide administration and after 1 g of acetazolamide administered‐ at 5 and 10 minutes intervals. Cerebral angiography was typically performed via transfemoral approach utilizing a dual plane digital subtraction (DSA) radiographic angiographic system. CT angiograms were utilized if DSA was not available. Results The study included 32 patients, predominantly with unilateral disease. A significant correlation was found between AC‐ASL adjusted steal percent and angiographic ACCT (r = ‐0.345, p=0.049), which was stronger when comparing the ratio of ACCT between occlusive and nonocclusive hemispheres (r = ‐0.40, p=0.020). No significant correlation was found with SSSE nor angiographic collateralization patterns. Conclusion AC‐ASL can non‐invasively evaluate arteriocapillary circulation time, comparable to catheter angiography in patients with steno‐occlusive disease. This suggests AC‐ASL is useful for assessment of CVR in patients, providing a safe and non‐invasive methodology.

Abstract 367: Physiologic steal in white matter structures of non‐flow limited cerebral hemispheres as evidenced by observations of acetazolamide challenge arterial spin labeling MR

Background Acetazolamide administration can allow for comparisons between cerebral blood flow (CBF) at baseline and after acetazolamide challenge to evaluate the cerebral vasculature. While effects of augmentation have been studied in vaso‐occlusive hemispheres, little has been reported on physiologic, non‐flow limited hemispheres. Methods Patients who underwent acetazolamide challenge MRI from 2014‐2021 and a cerebral angiogram within one year were included. Patients with bilateral disease or non‐diagnostic imaging artifacts were excluded. MRIs were obtained after 1 g of acetazolamide administered 5 and 10 minutes prior to acquisition. Augmentation and steal maps were generated by comparing pre and post acetazolamide CBF images. Regression analysis, Pearson correlation coefficient, two sample t‐Test, Spearman and Mann Whitney U analyses were utilized for statistical evaluation. Results 38 Patients with unilateral cerebral vaso‐occlusive disease underwent the acetazolamide challenge. Steal and T2 hyperintensities were assessed in non‐flow limited hemispheres (NFLH) and flow limited hemispheres (FLH). A moderate correlation was demonstrated between NFLH steal and NFLH T2 hyperintensities (rs=0.48, p=0.0020). A weak correlation without statistical significance was demonstrated between ipsilateral T2 and contralateral T2 hyperintensities (rs= .27, p=.10). No correlation was found between steal severity or T2 hyperintensity and occlusion locations of stenosis. Conclusion Vascular steal phenomenon was demonstrated in the distal cerebral vasculature of cerebral white matter even in the absence of upstream flow limiting stenosis, suggesting an inherit vulnerability of these structures to hemodynamic fluctuations and possible contributing etiology to leukoaraiosis.

A surge in fulminant idiopathic intracranial hypertension cases within 1 year from the coronavirus disease 2019 pandemic lockdown: A case series

Abstract PURPOSE: A surge in the number of cases of fulminant idiopathic intracranial hypertension (IIH) was observed within 1 year of the lockdown due to coronavirus disease 2019 (COVID-19) in March 2020. This study aims to describe the characteristics, outline of management, and final visual outcome for six cases diagnosed with fulminant IIH. METHODS: We reviewed the medical records of six adult patients diagnosed with fulminant IIH, between May and November 2021, based on their presentation at the University of Ottawa, Eye Institute. RESULTS: All six patients were diagnosed with fulminant IIH (five females and one male). Five out of six patients were obese and one patient was overweight. Medical treatment included the administration of acetazolamide (2–4 g/day) to all patients and intravenous methylprednisolone in four patients. Surgical treatment (optic nerve sheath fenestration) was performed for all patients. Visual function improved for three out of the six patients, two patients remained stable, and one patient got worse. CONCLUSION: There has been a recent surge in the number of cases of fulminant IIH in the COVID-19 lockdown period. The negative impact of COVID-19 on health led to an increase in weight, which is thought to have played a role in this recent increase in fulminant IIH cases. Urgent surgery, coupled with acetazolamide administration, is recommended for such patients. Patient compliance and close follow-up are recommended for early detection of relapse.

The effect of systemic acetazolamide administration on intraocular pressure in healthy horses-A preliminary study.

In equine glaucoma, topical treatment with carbonic anhydrase inhibitors (CAIs) is recommended. Oral acetazolamide, a systemic CAI, is used in horses with hyperkalemic periodic paralysis. Information regarding its effect on equine intraocular pressure (IOP) is scarce. The aim of the study was to determine the effect of oral acetazolamide treatment on IOP in horses, in a case-control study. Ten healthy horses. Horses were treated with oral acetazolamide (4.4 mg/kg) BID for 1 week. Serum acetazolamide concentrations were determined by liquid chromatography/tandem mass spectrometry, and IOP were measured before treatment, daily during treatment, and at 48 and 72 h after treatment. Acetazolamide serum levels reached steady state at 72 h after the first oral dose. In a mixed effect model logistic regression, there was a significant decrease in IOP on the third treatment day, of 2.4 mmHg (p = .012) and 2.7 mmHg (p = .006) in the left (OS) and right eye (OD), respectively. On the seventh day, there was a decrease in 2.5 mmHg (p = .008) and 2.7 mmHg (p = .007) OS and OD, respectively. A significant increase occurred 48 h following treatment discontinuation (3.6 mmHg, p < .001 and 3.5 mmHg, p < .001 OS and OD, respectively). The area under the concentration versus time curve (AUC(0-10h)) was 1.1 ± 0.5 μg/mL*h, mean residence time 6.7 ± 4.3 h, peak plasma concentration (Cmax) 0.4 ± 0.4 μg/mL and time to reach Cmax 1.8 h. There was a significant increase in serum concentrations 1, 2, 48, 72, and 156 h following the first drug administration (p < .05). Further studies are required to determine whether acetazolamide is a potential treatment for equine glaucoma.

Diuresis Efficacy in Ambulatory Congested Heart Failure Patients: Intrapatient Comparison of 3 Diuretic Regimens (DEA-HF)

BackgroundLimited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients. ObjectivesThe authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients. MethodsA prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250 mg; IV furosemide 250 mg plus oral metolazone 5 mg; and IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments were administered once a week, in 1 of 6 randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation. ResultsA total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4,691 mg (95% CI: 4,153-5,229 mg) compared with furosemide alone, 3,835 mg (95% CI: 3,279-4,392 mg; P = 0.015) and to furosemide plus acetazolamide 3,584 mg (95% CI: 3,020-4,148 mg; P = 0.001). Furosemide plus metolazone resulted in 1.84 L of urine (95% CI: 1.63-2.05 L), compared with 1.58 L (95% CI: 1.37-1.8); P = 0.039 collected following administration of furosemide plus acetazolamide and 1.71 L (95% CI: 1.49-1.93 L) following furosemide alone. The incidence of worsening renal function was significantly higher when adding metolazone (39%) to furosemide compared with furosemide alone (16%) and to furosemide plus acetazolamide (2.6%) (P < 0.001). ConclusionsIn ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared with IV furosemide alone or furosemide plus acetazolamide.

Recurrent unilateral corneal edema in a 54-year-old patient after endurance sports in low temperature

Introduction: Corneal edema in endurance sports at low temperatures is a rare occurrence, and few reports can be found in the literature. Patient and Clinical Findings: A case of unilateral corneal edema in a 54-year-old man with a history of laser in situ keratomileusis surgery, cataract surgery, and vitrectomy is presented. Recurrent episodes of corneal edema were observed during endurance cycling in temperatures below 10 °C, with complete recovery observed the next day without any treatment. Diagnosis, Interventions, and Outcomes: Pathophysiology and therapeutic strategies were discussed. Local administration of hyperosmolar saline lacked of any effect as did administration of acetazolamide. A protection of the affected eye by contact lens was not successful, but ski goggles could effectively prevent the corneal edema. Conclusions: Some single reports in the literature described roughly similar corneal findings under different conditions. A systematic evaluation of this case could reveal a fateful combination of cold temperature, physical activity, and susceptibility of the corneal endothelium. Protection from cold wind by ski goggles was found to be an effective practical approach.

Abstract TP139: Revascularization Improves Vascular Hemodynamics in Pediatric Moyamoya Patients

Introduction: Cerebrovascular reactivity (CVR) reflects the change in cerebral blood flow (CBF) in response to vasodilation. Studies have demonstrated that impaired CVR was associated with a higher risk of acute stroke in patients with intracranial vasculopathy and that bypass surgeries can reduce the risk of strokes. Moyamoya disease is a progress cerebrovascular disorder that begins during childhood. Arterial spin labeling (ASL) is a quantitative MRI technique for non-invasive CBF and CVR measurement; ASL with multiple delays can also measure arterial transit time (ATT). Here, we compare the CBF, CVR, and ATT in pediatric Moyamoya patients before and after bypass using multi-delay ASL. Hypothesis: CVR will increase significantly after bypass surgeries. Methods: Imaging data were acquired from 22 Moyamoya patients (11 months - 18 years, 14 females) using a 3T MRI system. All patients had unilateral or bilateral occlusion at ACA, MCA and/or PCA. Multi-delay ASL data (7 delays) were acquired at baseline and 15 minutes after acetazolamide administration. CBF and ATT were computed using the general kinetic model. CVR was computed as the percentage of CBF change compared with baseline CBF. Flow territories (right and left ACA, MCA, and PCA) were defined using the Harvard-Oxford atlases. Paired t-tests were conducted to compare the mean CVR, CBF, and ATT changes before and after bypass surgeries. Results: The figure shows the hemodynamic maps of an example patients. Overall, CVR and CBF in the affected regions increased after bypass; ATT in these regions decreased after bypass. For this cohort, our analysis showed that CVR of the affected regions increased significantly by 68% and ATT reduced significantly by 10.7% measured by multi-delay ASL, implying improved circulation and lower risk for strokes. Discussion: Multi-delay ASL was effective to detect improved CVR and reduced ATT in pediatric Moyamoya patients after bypass surgeries.

Acetazolamide –friend to foe

Bilateral acute angle closure attacks are rare and usually secondary to drugs or concurrent microspherophakia. Acetazolamide, a sulphonamide medication used in controlling intraocular pressure, is known to cause uveal effusion precipitating secondary acute angle closure attack. Here we report a well-documented case of concurrent bilateral angle closure with shallowing of the anterior chamber, supra-ciliary effusion, and serous and hemorrhagic choroidal detachment after administration of oral acetazolamide that resolved on withdrawing the insulting agent.

Effect of different hypoxic and hypobaric interventions on blood gas and erythrocyte-related indicators in rats.

To explore the effects of hypoxic and hypobaric conditions on blood gas and erythrocyte-related indicators in rats. SD male rats were exposed to low-pressure hypoxic conditions simulating an altitude of 6500 m in a small or a large experimental cabin. Abdominal aortic blood samples were collected and blood gas indicators, red blood cells (RBCs) count, and hemoglobin (Hb) content were measured. The effects of exposure to different hypoxia times, different hypoxia modes, normal oxygen recovery after hypoxia, and re-hypoxia after hypoxia preconditioning on blood gas indicators, RBCs count and Hb content were investigated. The effect of blood gas indicators was correlated with the length of exposure time of hypoxia and the reoxygenation after leaving the cabin. Hypoxia caused acid-base imbalance and its severity was associated with the duration of hypoxia; hypoxia also led to an increase in RBCs count and Hb content, and the increase was also related to the time exposed to hypoxia. The effects of reoxygenation on acid-base imbalance in rats caged in a small animal cabin were more severe that those in a large experimental cabin. Acetazolamide alleviated the effects of reoxygenation after leaving the cabin. Different hypoxia modes and administration of acetazolamide had little effect on RBCs count and Hb content. Normal oxygen recovery can alleviate the reoxygenation and acid-base imbalance of hypoxic rats after leaving the cabin and improve the increase in red blood cell and hemoglobin content caused by hypoxia. The improvement of hypoxia preconditioning on post hypoxia reoxygenation is not significant, but it can alleviate the acid-base imbalance caused by hypoxia in rats and to some extent improve the increase in red blood cell and hemoglobin content caused by hypoxia. Due to excessive ventilation and elevated RBCs count and Hb content after hypoxia reoxygenation, oxygen partial pressure and other oxygenation indicators in hypoxic rats are prone to become abnormal, while blood gas acid-base balance indicators are relatively stable, which are more suitable for evaluating the degree of hypoxia injury and related pharmacological effects in rats.

Acétazolamide et effusion uvéale : à propos de deux cas

We report two cases of uveal effusion following oral acetazolamide administration: one case after a standard cataract surgery and a second following a preventive treatment for altitude sickness. The outcome in both cases was favorable. This rare complication requires appropriate management, including ruling out other pathologies. The pathophysiological mechanism is not fully understood.

Acetazolamide and topiramate lower intracranial pressure through differential mechanisms: The effect of acute and chronic administration.

Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate. Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions. We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes. Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.

Possible strategies to reduce altitude-related excessive polycythemia.

We sought to determine the effects of three treatments on hemoglobin (Hb) levels in patients with chronic mountain sickness (CMS): 1) descent to lower altitude, 2) nocturnal O2 supply, 3) administration of acetazolamide. Nineteen patients with CMS living at an altitude of 3,940 ± 130 m participated in the study, which consisted of a 3-wk intervention phase and a 4-wk postintervention phase. Six patients spent 3 wk at an altitude of 1,050 m (low altitude group, LAG), six received supplemental oxygen for 12 h overnight (oxygen group, OXG), and seven received 250 mg of acetazolamide daily (acetazolamide group, ACZG). Hemoglobin mass (Hbmass) was determined using an adapted carbon monoxide (CO) rebreathing method before, weekly during, and 4 wk postintervention. Hbmass decreased by 245 ± 116 g (P < 0.01) in the LAG and by 100 ± 38 g in OXG, and 99 ± 64 g in ACZG (P < 0.05, each), respectively. In LAG, hemoglobin concentration ([Hb]) decreased by 2.1 ± 0.8 g/dL and hematocrit by 7.4 ± 2.9% (both P < 0.01), whereas OXG and ACZG only trended toward lower values. Erythropoietin concentration ([EPO]) decreased between 81 ± 12% and 73 ± 21% in LAG at low altitude (P < 0.01) and increased by 161 ± 118% 5 days after return (P < 0.01). In OXG and ACZG, the [EPO] decrease was ∼75% and ∼50%, respectively, during the intervention (P < 0.01). Descent to low altitude (from 3,940 m to 1,050 m) is a fast-acting measure for the treatment of excessive erythrocytosis in patients with CMS, reducing Hbmass by 16% within 3 wk. Nighttime oxygen supplementation and daily acetazolamide administration are also effective, but reduce Hbmass by only 6%.NEW & NOTEWORTHY To our knowledge, this is the first study examining the effect of three different treatments [descending to lower altitude (from 3,900 m to 1,050 m), nocturnal oxygen supply, and administration of acetazolamide] on changes in hemoglobin mass in patients experiencing chronic mountain sickness (CMS). We report that descent to low altitude is a fast-acting measure for the treatment of excessive erythrocytosis in patients with CMS, reducing Hbmass by 16% within 3 wk. Nighttime oxygen supplementation and daily acetazolamide administration are also effective, but reduce Hbmass by only 6%. In all three treatments, the underlying mechanism is a reduction in plasma erythropoietin concentration due to higher oxygen availability.

Premedication with acetazolamide: Is its use for postoperative pain and stress control after laparoscopic ovariectomy in dogs ruled out?

Studies in human medicine have concluded that acetazolamide reduces pain associated with carbon dioxide insufflation during laparoscopic surgery. However, there are no published reports regarding the use of acetazolamide for this purpose in companion animals, despite the increasing popularity of laparoscopic techniques in veterinary medicine due to their advantages over open surgeries. Thirty mixed-breed female dogs were included in the study and randomly assigned to one of three groups: OVE (median celiotomy ovariectomy; n = 10), OVEL (laparoscopic ovariectomy, n = 10) and OVELA (laparoscopic ovariectomy with acetazolamide preoperative administration; n = 10). Experienced surgeons performed all procedures, and the anaesthetic and analgesic protocols were identical for all animals. Acetazolamide was administered orally (at a dose of 25 mg/kg) 2 h prior to induction in the OVELA group. Postoperative pain was evaluated using serum cortisol, salivary cortisol, and the University of Melbourne Pain Scale (UMPS) Score. Any statistical differences were observed in the UMPS scores when the OVELA group was compared to the OVEL group at 1 h after surgery (p = 0.515), 12 h (p = 0.375) and 24 h (p = 0.242). Animals undergoing open surgery (OVE group) had significantly higher pain scores at all times after surgery when compared with OVEL and OVELA groups. A high positive correlation (r = 0.792; p = 0.01) was found between serum and saliva cortisol concentrations. Mean saliva cortisol concentration was not significantly lower for the OVELA group compared to the other groups. This study found evidence that preoperative administration of acetazolamide may be beneficial in managing postoperative pain in dogs after laparoscopic surgeries. However, further research with a larger sample size is needed to confirm this and to determine if acetazolamide should be included in a multimodal postoperative analgesia protocol for laparoscopic ovariectomy in dogs.

Vascular function in women: when studying perimenopause is peri important.

Vascular function in women: when studying perimenopause is peri important.

Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL. We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke. They underwent quantitative single-photon emission computed tomography using an autoradiographic method at rest and after acetazolamide (ACZ) administration. Regional cerebral blood flow (rCBF) in the cerebral cortex, lenticular nucleus, thalamus, and cerebellum was measured. We compared the rCBF parameters between patients with and without stroke. The baseline characteristics and magnetic resonance imaging findings were similar between the two groups, except for a higher frequency of pyramidal tract sign (75% vs. 0%) and a larger number of old lacunes (15.4 ± 8.8 vs. 2.2 ± 1.8) in the patients with stroke. Of the rCBF parameters measured, significantly lower flow (mL/100 g/min) was observed in ACZ-rCBF in the thalamus (35.6 ± 9.4 vs. 51.1 ± 7.6, p = 0.01) and ΔrCBF in the thalamus (10.6 ± 3.7 vs. 21.0 ± 7.9, p = 0.02) in the patients with stroke. Cerebrovasoreactivity in the thalamus was significantly associated with stroke in patients with CADASIL.

Use Acetazolamide in the Complex Therapy of Alzheimer's Disease.

Impaired glymphatic clearance is one of the causes of Alzheimer's disease. Acetazolamide is a drug that affects the normalization of glymphatic clearance. We followed four women aged 65-70 years with a diagnosis of Alzheimer's disease in 2019-2021. They were treated in the unit according to Alzheimer's disease treatment standards. During periodic examination by an ophthalmologist, they were diagnosed with first-stage glaucoma (initial) - a blind spot interfering with normal peripheral vision and a deepening of the optic disc in the central zone were identified. For a glaucoma treatment, they were prescribed Acetazolamide 125 mg once a day in the morning for 7 days with weekly monitoring of intraocular pressure. They also received Asparkam, 1 tablet, 3 times a day during Acetazolamide administration to prevent a deficiency of potassium ions in the body. On days 12-14 after normalization intraocular pressure, Acetazolamide administration was discontinued. To monitor the dynamics of cognitive impairment, patients on the unit underwent Trail Making Test Parts A & B paper-pencil versions every month. Before glaucoma treatment, the patients' Trail Making Test Parts A speeds were 84, 87, 90, and 92 seconds. The speed of Part B was 270, 300, 293, and 305 seconds. After two weeks of glaucoma treatment, patients again completed the Trail Making Test Parts A & B paper-pencil versions. The patients' speeds for Part A were 60, 68, 63, and 70 seconds. The speeds in Part B were 180, 190, 217, and 194 seconds. Administration of Acetazolamide has a positive effect on patients with cognitive deficits and can be successfully used as part of the complex therapy of Alzheimer's disease.

Cerebral Oxygen Metabolism in Patients with Mild and Severe Sickle Cell Disease and Thalassemia

Introduction Studies in patients with severe (HbSS and HbSβ0) sickle cell disease (SCD) have reported reduced oxygen metabolism compared to controls despite the preserved oxygen delivery (OD). Whereas previous studies have found similar lesion load in mild SCD patients (HbSC and HbSβ+), oxygen metabolism has not been studied in this group. Interestingly, we previously showed that CBF values in mild SCD patients were lower compared to severe SCD, and comparable with healthy controls. Here, we assessed the OD, oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2) and lesion volumes in adult patients with severe and mild SCD and compared our results with thalassemia patients as anemic controls and healthy controls. In addition, the effect of a vasodilatory stimulus on the cerebral parameters was studied to test if increased CBF influences oxygen consumption. Methods In this study, 75 patients with severe SCD (64 HbSS and 11 HbSβ0), 26 patients with mild SCD (16 HbSC and 10 HbSβ+), 17 patients with thalassemia (7 NTDT and 10 TDT) and 30 healthy controls were included. Venous blood T2 was measured using T2-Relaxation-Under-Spin-Tagging (TRUST). Whole brain (WB) CBF was measured using time-encoded pseudo-continuous ASL (te-ASL). TRUST and te-ASL scans were performed before and after acetazolamide (ACZ) administration as a vasodilatory stimulus. Fluid-Attenuated Inversion Recovery (FLAIR) scans were acquired for the assessment and segmentation of lesions. OEF was calculated from arterial saturation measured by pulse oximetry and venous saturation calculated from blood T2 using a sickle cell-specific calibration model and a healthy control model. CMRO2 was calculated from the WB CBF, OEF and oxygen content (calculated from hemoglobin and arterial saturation). To test the effect of ACZ-induced vasodilation, ∆CBF, ∆OD, ∆OEF and ∆CMRO2 were calculated. A one-way analysis of covariance (ANCOVA) was conducted (or a nonparametric alternative) with posthoc Bonferroni correction to test for statistically significant differences in cerebral parameters between the participating groups controlling for age and sex. For ∆CBF, ∆OD, ∆OEF and ∆CMRO2, baseline values were added as additional covariates. Results CBF was significantly higher in severe SCD compared to other groups and significantly higher in thalassemia patients compared to mild SCD and healthy controls (Table 1). No significant differences were found in OD between the groups. OEF was significantly lower in severe SCD patients compared to other groups and significantly lower in thalassemia patients compared to mild SCD patients and healthy controls (Table 1). CMRO2 was significantly lower in severe SCD and thalassemia patients compared to mild SCD patients and healthy controls (Table 1). ∆CBF upon ACZ administration was not significantly different between the groups. ∆OD was significantly higher in controls compared to severe SCD and thalassemia patients (Table 1). Infusion of ACZ impaired the OEF and CMRO2 more in severe SCD compared to the other groups (Table 1: ∆OEF and ∆CMRO2). Lesion volume was significantly larger in the severe SCD group compared to the healthy controls but no significant differences were found between the other groups (Fig. 1). Conclusion Our results show that OEF and CMRO2 were significantly higher in mild SCD patients, and no different from healthy controls, compared to severe SCD and thalassemia patients, illustrating a more balanced oxygen supply versus demand in these less anemic patients. Furthermore, the finding that ACZ-induced elevated CBF significantly reduced the CMRO2 in severe SCD, but not in the other groups, suggests that functional shunting may play a role in severely affected SCD patients. Despite the large differences in cerebral oxygen metabolism between severe and mild SCD, no difference in lesion volume could be observed between these groups. One possible mechanism that might be responsible for the lesion load in mild SCD patients could be the higher blood viscosity in this group that has been hypothesized to cause other complications such as retinopathy, particularly in patients with HbSC. Another explanation could be that lesion volume is more related to deep brain hypoxia than whole brain oxygen metabolism which could be confirmed by further studies investigating deep brain oxygenation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Capillary transit time heterogeneity inhibits cerebral oxygen metabolism in patients with reduced cerebrovascular reserve capacity from steno-occlusive disease

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO2), or if some patients demonstrate reduced CMRO2 related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO2 were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO2 after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.