Search Results (139)

Background: Episodic ataxia type 2 (EA2) is the most common subtype of episodic ataxia and is primarily caused by pathogenic variants in the CACNA1A gene. Although classically characterized by paroxysmal ataxia, CACNA1A-related disorders are increasingly recognized as an age-dependent phenotypic continuum that extends beyond episodic cerebellar dysfunction to include fluctuating weakness, persistent neurological signs, and neurodevelopmental impairments. Case report: A 12-year-old boy presented with episodic vertigo. His medical history was notable for infantile paroxysmal tonic upward gaze beginning at 6 months of age. From the age of 7 years, he developed frequent episodes of vertigo and ataxia lasting 2 to 3 h. At 10 years of age, he experienced an episode of acute lower limb weakness with diminished deep tendon reflexes, without prominent ataxia. Guillain–Barré syndrome was initially suspected, and he received two courses of intravenous immunoglobulin, with only transient improvement. Neurophysiological studies were largely unremarkable, except for an isolated decremental response on repetitive nerve stimulation. In addition to paroxysmal events, he exhibited persistent interictal cerebellar signs, including dysmetria, dysdiadochokinesia, and downbeat nystagmus. Neuropsychological testing revealed mild intellectual disability with prominent visuospatial deficits. Trio-based whole-exome sequencing identified a de novo CACNA1A splice donor variant (c.978 + 1G > A), confirming the diagnosis of EA2. Treatment with acetazolamide resulted in marked improvement in episodic ataxic events. Conclusions: This case highlights EA2 as part of a broader CACNA1A-related phenotypic continuum rather than a purely paroxysmal disorder. Awareness of atypical and age-dependent manifestations is crucial to avoid diagnostic pitfalls and to facilitate the timely initiation of targeted therapy and appropriate developmental support. Full article

Background and Clinical Significance: Acetazolamide is routinely used post-cataract surgery to prevent intraocular pressure (IOP) spikes. Rare non-cardiogenic pulmonary edema (NCPE) cases highlight its risks in elderly comorbid patients. This report details acetazolamide-induced NCPE and provides a review of current evidence from the literature. Case Presentation: A 74-year-old male with chronic kidney disease, atrial fibrillation, and aortic aneurysm repair received 250 mg oral acetazolamide post-cataract extraction. Clinical, imaging, and lab data were documented during Intensive Care Unit (ICU) stay. PubMed/Google Scholar review identified similar cases. Within 30 min, severe hypoxemia with SpO₂ (peripheral oxygen saturation) of 77%, accompanied by tachypnea and hypertension, necessitated endotracheal intubation. Echocardiography showed preserved left ventricular (LV) function; computed tomography (CT) confirmed bilateral alveolar opacities without cardiomegaly or embolism, indicating permeability-mediated NCPE. Lung-protective mechanical ventilation and vasopressor therapy resulted in hemodynamic and respiratory stabilization. On day 4, ventilator-associated pneumonia (VAP) due to Acinetobacter baumannii resolved with targeted antibiotic therapy. The patient made a full recovery following ICU discharge. To date, nine prior cases have been reported, alongside 31 entries in EudraVigilance reflecting a 19.4% mortality rate. Conclusions: Rapid-onset NCPE from acetazolamide involves endothelial injury, distinct from cardiogenic pulmonary edema. Early recognition, drug cessation, and admission to the intensive care unit (ICU) are vital components of therapeutic intervention. Risk stratification and pharmacovigilance are recommended for perioperative safety. Full article

The essential reaction of CO₂ hydration, fundamental to all living organisms, is facilitated by the enzyme carbonic anhydrase (CA, EC 4.2.1.1). This enzyme plays a crucial role in regulating various physiological and pathological processes. A series of heterocyclic benzenesulfonamide derivatives (19 compounds) were evaluated as possible inhibitors of human CAs. Their inhibitory properties were tested against several isoforms such as the cytosolic hCA I and hCA II, as well as the transmembrane isoforms hCA IV, hCA IX and hCA XII. The tested molecules demonstrated notable inhibitory potential, particularly toward hCA II and hCA IV, where five and four compounds, respectively, exhibited greater potency than the reference inhibitor, acetazolamide. Molecular docking simulations were further performed to elucidate the binding interactions of the most active compounds with the human CA II, IV IX and XII isoforms Full article

Background: Vascular disease is a known risk factor for the development of leukoaraiosis. Assessment of cerebral blood flow (CBF) was performed at baseline and after acetazolamide (AZM) challenge to evaluate for vascular reserve and steal within the brain. Little has been reported on the physiological reserve in the non-flow-limited hemispheres. This study attempts to evaluate for vascular steal in areas commonly involved in leukoaraiosis, in the setting of pharmaceutically induced states of increased CBF. Methods: Patients who underwent AZM challenge MRI from 2014 to 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 AZM was administered 5 and 10 min prior to acquisition. Augmentation and steal maps were generated. Regression analysis, Pearson correlation coefficient, two-sample t-test, Spearman and Mann–Whitney U analyses were utilized for statistical evaluation. Results: A total of 38 patients with unilateral cerebral vaso-occlusive disease underwent the AZM challenge. Vascular 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 = 0.27, p = 0.10). Conclusions: The 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 inherent vulnerability of these structures to hemodynamic fluctuations and possiblly contributing etiology to leukoaraiosis. Full article

Obesity hypoventilation syndrome (OHS) is a severe and underrecognized respiratory disorder characterized by the coexistence of obesity, daytime hypercapnia, and sleep-disordered breathing. Although well described in adults, pediatric OHS remains poorly defined despite the rising prevalence of childhood obesity. Its pathophysiology is multifactorial, involving obesity-related mechanical constraints, impaired ventilatory control, altered chemosensitivity, and frequent overlap with obstructive sleep apnea. Clinical manifestations in children are often subtle and nonspecific, including snoring, sleep fragmentation, daytime sleepiness, and neurocognitive impairment, frequently leading to delayed diagnosis and, in some cases, acute cardiopulmonary decompensation. Management of pediatric OHS is challenging and largely extrapolated from adult data. Positive airway pressure therapy remains the cornerstone of treatment, while weight reduction is essential but difficult to achieve in pediatric populations. Pharmacological approaches such as medroxyprogesterone or acetazolamide remain experimental, with limited pediatric evidence. This review synthesizes current knowledge on pediatric OHS, focusing on epidemiology, pathophysiology, clinical presentation, diagnostic challenges, and therapeutic strategies. Increased awareness and earlier recognition are essential to prevent progression to chronic respiratory failure and long-term cardiovascular complications. Full article

Background: Among the 15 human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms, hCA IX and XII are particularly important due to their roles in tumor cell growth and survival, identifying them as promising targets for anticancer therapy. As a result, considerable effort has been directed toward the development of novel inhibitors that are highly selective for these isoforms. Methods: A library of twelve novel N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carbothioamides 3 along with two new N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carboxamide derivatives 5 were synthesized and their inhibition abilities were tested against four human carbonic anhydrase isozymes (hCA I, II, IX and XII) related to some global diseases including glaucoma, cancer and osteoporosis. Results: All compounds exhibited potent inhibition of the tested isoforms in the nanomolar range. Compound 3i showed the highest inhibition of hCA I activity but demonstrated poor selectivity toward the other isoforms. Compound 3h displayed superior selectivity for hCA II over hCA I (hCA I/II = 37) and exhibited 2.5-fold higher inhibitory activity compared to acetazolamide (AAZ). Among the tested compounds, 3l (K_i = 32.1 nM) demonstrated markedly improved selectivity for hCA IX over hCA I, II, and XII relative to the standard drug. Notably, compound 3a showed the most potent inhibition against hCA XII (K_i = 6.8 nM), comparable to AAZ, while exhibiting significantly greater selectivity over off-target isoforms and the other tumor-associated isozyme (hCA IX/XII = 20 versus hCA IX/XII = 4.5 for AAZ). Conclusions: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity. Full article

Background: Descemet membrane endothelial keratoplasty (DMEK) is the most frequently performed keratoplasty procedure in many countries. One of the most common early complications is an elevation of intraocular pressure (IOP). The aim of this study was to characterize early postoperative IOP behavior following DMEK performed with 10% sulfur hexafluoride (SF₆) tamponade and to determine the frequency and timing of required IOP-lowering interventions within the first 48 h. Methods: We retrospectively reviewed postoperative outcomes of 116 consecutive DMEK procedures between May and December 2024 at the University Medical Center in Mainz, Germany. No specific exclusion criteria were applied. All surgeries included a surgical iridectomy at the 6 o’clock position, 10% (SF₆) tamponade, and maintaining a mid-normal IOP at the end of surgery. Postoperative assessments included IOP measured using Goldmann applanation tonometry, the percentage of gas fill in the anterior chamber evaluated at the slit lamp, and the need for IOP-lowering interventions as determined by the on-call resident at 3, 24, and 48 h after surgery. IOP-lowering interventions consisted of venting in cases of elevated IOP, gas fill > 90%, and/or suspected angle closure or pupillary block, as well as intravenous or oral acetazolamide in cases of moderate IOP elevation with a lower gas fill and a patent iridectomy. If a single intervention was insufficient, a combined approach was used. Results: A total of 116 eyes from 98 patients (62 female, mean age 73.0 ± 9.8 years) were analyzed. DMEK was combined with cataract surgery in 41 eyes, and 4 eyes underwent phakic DMEK. Postoperatively, all iridectomies remained patent, and no cases of pupillary block occurred. Mean IOP and gas fill were within normal limits and declined steadily during the first 48 h. IOP-lowering procedures were performed in 11 eyes (9.5%), including venting (n = 3), acetazolamide administration (n = 7), and a combination of both (n = 1). There was no difference between DMEK and triple-DMEK regarding postoperative gas fill, IOP, or the need for IOP-lowering interventions. Mean postoperative IOP was significantly higher, and IOP-lowering interventions were more frequent in glaucoma vs. non-glaucoma patients. Re-bubbling was performed in 12 eyes (10.3%). Two cases of primary graft failure (1.7%) were recorded. Conclusions: In our patient cohort, a standardized surgical approach incorporating a surgical iridectomy at the 6 o’clock position, 10% SF₆ tamponade, and maintaining a mid-normal IOP at the end of surgery effectively prevented pupillary block. We recommend early postoperative assessment of IOP and percent gas fill to promptly identify and manage impending IOP elevation, which is particularly important in patients with glaucoma. Full article

Bacterial carbonic anhydrases (CAs) are essential for intracellular pH regulation, bicarbonate homeostasis, and energy metabolism, making them attractive antimicrobial targets. Here, building on evidence that acetazolamide (AZA) delivered via hyaluronic acid–palmitate (HA-PA) nanocarriers impairs Escherichia coli growth and its glucose uptake, we investigated the physiological roles of β- and γ-class CAs using sulphonamide inhibitors with distinct selectivity encapsulated in HA-PA nanomicelles to ensure intracellular delivery. AZA, a potent dual β/γ-CA inhibitor, ethoxzolamide (EZA), a selective β-CA inhibitor, and hydrochlorothiazide (HCT), a weaker inhibitor of both classes, were tested for effects on bacterial physiology. The nanoparticles reduced growth in a dose- and class-dependent manner, with AZA exerting the strongest activity, EZA intermediate inhibition, and HCT only modest effects at higher concentrations. Early metabolic responses assessed via intracellular ATP after three hours of exposure revealed an unexpected and reproducible ATP increase for all inhibitors relative to untreated cells, suggesting reduced ATP consumption in bicarbonate-dependent pathways. These findings provide indirect yet compelling evidence that β- and γ-class CAs influence bacterial energy homeostasis and support the rationale for CA inhibition as an antimicrobial strategy, while highlighting HA-PA carriers as effective systems for delivering CA inhibitors intracellularly and enhancing their functional activity in bacterial cells. Full article

High-altitude exposure poses significant health challenges to mountaineers, military personnel, travelers, and indigenous residents. Altitude-related illnesses encompass acute conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), and chronic manifestations like chronic mountain sickness (CMS). Hypobaric hypoxia induces oxidative stress and inflammatory cascades, causing alterations in multiple organ systems through co-related amplification mechanisms. Therefore, this review aims to systematically discuss the injury mechanisms and comprehensive intervention strategies involved in high-altitude diseases. In summary, these pathologies involve key damage pathways: oxidative stress activates inflammatory pathways through NF-κB and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes; energy depletion impairs calcium homeostasis, leading to cellular calcium overload; mitochondrial dysfunction amplifies injury through mitochondrial permeability transition pore (mPTP) opening and apoptotic factor release. These mechanisms could be converged in organ-specific patterns—blood–brain barrier disruption in HACE, stress failure in HAPE, and right heart dysfunction in chronic exposure. Promising strategies include multi-level therapeutic approaches targeting oxygenation (supplemental oxygen, acetazolamide), specific pathway modulation (antioxidants, calcium channel blockers, HIF-1α regulators), and damage repair (glucocorticoids). Notably, functional foods show significant therapeutic potential: dietary nitrates (beetroot) enhance oxygen delivery, tea polyphenols and anthocyanins (black goji berry) provide antioxidant effects, and traditional herbal bioactives (astragaloside, ginsenosides) offer multi-targeted organ protection. Full article

Background: COPD patients may be prone to cerebral small vessel disease resulting in perivascular white matter lesions and consequent cognitive decline. The pathophysiological background of these observations is not completely understood. It is hypothesized that COPD may involve systemic vascular dysfunction extending to the brain. The present study aimed to assess whether acetazolamide-induced cerebral vasoreactivity and cerebrovascular reserve capacity are impaired in patients with COPD. Methods: A total of 17 patients with COPD and 20 healthy control subjects underwent transcranial Doppler monitoring before and after IV administration of 15 mg/kgBW acetazolamide for 20 min. Cerebrovascular reactivity (CVR) was defined as a percent increase in blood flow velocity in the middle cerebral artery (MBFV) after acetazolamide. Cerebrovascular reserve capacity (CVRC) was defined as the maximal percent change in MBFV during the entire registration. Results: Administration of acetazolamide resulted in a slight decrease in pH and a mild increase in PaCO₂ (both p < 0.001) in COPD patients. Absolute MBFV values were consequently higher, and pulsatility indices were lower in control subjects compared to those measured in patients with COPD. The CVR at different time points after acetazolamide and CVRC did not show any difference between COPD patients and control subjects. Conclusions: In the present study, in normocapnic mild and normocapnic moderate COPD patients, cerebrovascular reactivity is not impaired, indicating that in mild stages, cerebral arteriolar function is preserved. Further studies, using patient selection based on different severity stages of the disease, may show whether alteration of the cerebral arteriolar function is responsible for the white matter lesions and cognitive decline observed in severe COPD patients. Full article

Background: Fulminant idiopathic intracranial hypertension (IIH) is a rare and vision-threatening variant of IIH, characterized by rapid visual deterioration and a high risk of irreversible blindness. Urgent intervention is required to prevent permanent optic nerve damage. Cerebral transverse venous stenting (CTVS) has emerged as an effective treatment for medically refractory IIH, but data on its use in fulminant cases remain limited. Methods: A retrospective consecutive cohort study was conducted at a tertiary center and included all patients with fulminant IIH diagnosed by modified Dandy criteria, with bilateral transverse sinus stenosis > 50% and a trans-stenotic pressure gradient ≥ 8 mmHg on venography. Before stenting, patients received high-dose acetazolamide (up to 3000 mg/day) and IV methylprednisolone (1000 mg/day × 3). Neuro-ophthalmic assessment included BCVA, Ishihara color vision, pupillary exam, disc edema grading, Humphrey visual fields, and optical coherence tomography (OCT). Follow-up occurred at baseline (admission), 1 week, 1 month, 3 months, and 12 months. Results: Five young female patients underwent successful CTVS without peri- or post-procedural complications. Significant improvement in headache and stabilization or recovery of visual function were observed in all patients. OCT revealed early retinal nerve fiber layer thinning within one week, preceding clinical resolution of papilledema. Conclusions: Emergent CTVS appears to be a safe and effective vision-preserving procedure in fulminant IIH, offering rapid intracranial pressure reduction and early neuro-ophthalmologic improvement. OCT may serve as a useful early predictor of treatment success, supporting its role in post-procedural monitoring. Larger prospective studies are warranted. Full article

Background/Objectives: Overcoming resistance to diuretics is extremely important in decompensated chronic heart failure (HF). The objective of this study was to assess the efficacy and safety of oral acetazolamide, in addition to standard therapy, in HF patients admitted to the hospital with decompensation requiring intravenous loop diuretic therapy. Methods: In this open-label, prospective, multicenter, randomized trial, we included 416 patients hospitalized with decompensated HF. The patients were randomized into two groups: (1) standard therapy, and (2) standard therapy + acetazolamide orally 250 mg 3 times a day in the first 3 days of hospitalization. At randomization, oral thiazide/thiazide-like and loop diuretics were stopped, and intravenous furosemide was initiated. Results: Successful decongestion within 72 h of randomization was observed in 82 patients (39.6%) in the acetazolamide group and in 83 patients (39.7%) in the standard therapy group (p = 0.983). There was a significant difference in the increase in diuresis in the first 72 h (p = 0.028) and in natriuresis on the 2nd day (p = 0.04). There were no differences between the groups in duration of stay in the intensive care unit, duration of index hospitalization, 6 min walk test distance, and clinical assessment scale scores. Death from any cause occurred in three (1.4%) patients in the acetazolamide group, and in the same number of patients in the standard therapy group (p = 0.996). Death from cardiovascular cause and due to decompensated HF also did not differ between the groups during follow-up. Conclusions: The addition of acetazolamide to standard therapy in decompensated chronic HF resulted in a higher cumulative urine output during the first 72 h and natriuresis on the 2nd day after randomization. Full article

Background: Transient intraocular pressure (IOP) elevations frequently occur after cataract surgery and may raise concerns, especially in patients susceptible to glaucomatous damage or pressure-related complications. These IOP spikes have also been linked to postoperative discomfort and headache. Oral acetazolamide is often used prophylactically, despite its known systemic side effects. Objectives: To evaluate the clinical benefit of routine prophylactic oral acetazolamide in reducing IOP after uncomplicated phacoemulsification performed with an anterior chamber maintainer (ACM). Methods: In this retrospective case–control study, 196 eyes from 196 patients were included. All underwent standard phacoemulsification with an ACM. Patients either received oral acetazolamide postoperatively (n = 98) or no IOP-lowering medication (n = 98). IOP was measured preoperatively, and on postoperative days one and seven. Results: On day one, mean IOP was 14.0 ± 3.8 mmHg in the acetazolamide group versus 15.4 ± 3.8 mmHg in controls (p < 0.005). By day seven, IOP was identical in both groups (13.5 mmHg), with no statistically significant difference (p = 0.95). No participant in either group reported headache or serious adverse effects, though 10% in the acetazolamide group experienced mild, transient systemic symptoms. Conclusions: In low-risk patients undergoing uneventful cataract surgery with ACM, routine use of oral acetazolamide yields only a modest, short-lived IOP reduction without evident clinical benefit. Its use may be unnecessary in this setting, though targeted prophylaxis could be considered for high-risk individuals. Full article

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article

Idiopathic intracranial hypertension (IIH) with (IIHWP) and without papilledema (IIHWOP) is characterized by increased cerebrospinal fluid (CSF) pressure and no evident cause, mostly affecting obese women of childbearing age and possibly leading to vision loss. However, in neonates, infants, and toddlers, these conditions remain understudied entities. This review investigates clinical features, risk factors, treatments, and outcomes to inform their care. From 2278 publications found in PubMed, 2974 in Scopus, and 1684 in the Web of Science Core Collection, 104 relevant articles were analyzed. Among 300 cases, 48.3% were male and 26.0% female, with 43.0% meeting the modified Dandy criteria. Typical signs and symptoms, besides papilledema (23.0%) or its absence (49.0%), included bulging fontanelle (67.7%), irritability (34.3%), vomiting (33.0%), and fever (18.3%). The most triggering factors were medications (35.3%) and infections (15.0%). The mean CSF opening pressure was 35.1 cm H₂O, ranging from 9.5 to 77 cm H₂O. Main treatment options were lumbar punctures (72.7%), discontinuation of triggering medications (26.3%), acetazolamide (18.7%), and corticosteroids (7.7%); 3.0% required shunting. Unlike in adults, males were more commonly affected, and papilledema was less frequent. Most cases resolved with conservative treatment. A nosological distinction between IIHWP and IIHWOP seems unlikely. Considering our findings and age-specific CSF pressure limits, new diagnostic criteria are proposed. Full article