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Cephalalgia : An International Journal... Apr 2021To review and discuss the clinical presentation and treatment of idiopathic intracranial hypertension. (Review)
Review
OBJECTIVE
To review and discuss the clinical presentation and treatment of idiopathic intracranial hypertension.
DISCUSSION
Visual alterations and headache are the two main symptoms of idiopathic intracranial hypertension, although additional features including cranial nerve palsies, cognitive deficits, olfactory deficits and tinnitus are not uncommon. The headache associated with idiopathic intracranial hypertension frequently has a migrainous phenotype. The underlying cause of the disorder has not yet been elucidated. Several hypotheses have been postulated but none of them can explain the full clinical picture. Therapeutic options remain limited, focusing mainly on reduction in body weight and the reduction of CSF production with carbonic anhydrase inhibitors.
CONCLUSION
The accurate diagnosis of idiopathic intracranial hypertension is essential as visual deterioration due to papilledema may be irreversible. Given its phenotypic similarity and frequent overlap with chronic migraine it is essential to consider idiopathic intracranial hypertension in the diagnostic workup of chronic headache; in particular, when considering its increasing prevalence. Understanding in detail the pathophysiological mechanisms behind the associated headache would also allow study of current and future therapeutic options in a structured way.
Topics: Acetazolamide; Analgesics; Headache; Headache Disorders; Humans; Intracranial Hypertension; Migraine Disorders; Papilledema; Pseudotumor Cerebri; Vision Disorders; Weight Reduction Programs
PubMed: 33631966
DOI: 10.1177/0333102421997093 -
Muscle & Nerve Apr 2018Periodic paralyses (PPs) are rare neuromuscular disorders caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs include hypokalemic... (Review)
Review
Periodic paralyses (PPs) are rare neuromuscular disorders caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs include hypokalemic paralysis, hyperkalemic paralysis, and Andersen-Tawil syndrome. Common features of PP include autosomal dominant inheritance, onset typically in the first or second decades, episodic attacks of flaccid weakness, which are often triggered by diet or rest after exercise. Diagnosis is based on the characteristic clinic presentation then confirmed by genetic testing. In the absence of an identified genetic mutation, documented low or high potassium levels during attacks or a decrement on long exercise testing support diagnosis. The treatment approach should include both management of acute attacks and prevention of attacks. Treatments include behavioral interventions directed at avoidance of triggers, modification of potassium levels, diuretics, and carbonic anhydrase inhibitors. Muscle Nerve 57: 522-530, 2018.
Topics: Acetazolamide; Andersen Syndrome; Anti-Arrhythmia Agents; Behavior Therapy; Carbonic Anhydrase Inhibitors; Diuretics; Diuretics, Potassium Sparing; Humans; Hydrochlorothiazide; Hypokalemic Periodic Paralysis; Paralyses, Familial Periodic; Paralysis, Hyperkalemic Periodic; Potassium
PubMed: 29125635
DOI: 10.1002/mus.26009 -
Muscle & Nerve Oct 2020The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1... (Review)
Review
The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation. In the absence of genetic confirmation, the diagnosis is supported by detailed electrophysiological testing, exclusion of other related disorders, and analysis of a variant of uncertain significance if present. Symptomatic treatment with a sodium channel blocker, such as mexiletine, is usually the first step in management, as well as educating patients about potential anesthetic complications.
Topics: Acetazolamide; Age of Onset; Carbonic Anhydrase Inhibitors; Chloride Channels; Electrodiagnosis; Electromyography; Fatigue; Genetic Testing; Humans; Lamotrigine; Mexiletine; Muscle Weakness; Muscle, Skeletal; Myalgia; Myotonia Congenita; Myotonic Disorders; NAV1.4 Voltage-Gated Sodium Channel; Practice Guidelines as Topic; Ranolazine; Sodium Channel Blockers; Voltage-Gated Sodium Channel Blockers
PubMed: 32270509
DOI: 10.1002/mus.26887 -
International Journal of Molecular... Feb 2020Aquaporin-4 (AQP4) is the main water channel protein expressed in the central nervous system (CNS). AQP4 is densely expressed in astrocyte end-feet, and is an important... (Review)
Review
Aquaporin-4 (AQP4) is the main water channel protein expressed in the central nervous system (CNS). AQP4 is densely expressed in astrocyte end-feet, and is an important factor in CNS water and potassium homeostasis. Changes in AQP4 activity and expression have been implicated in several CNS disorders, including (but not limited to) epilepsy, edema, stroke, and glioblastoma. For this reason, many studies have been done to understand the various ways in which AQP4 is regulated endogenously, and could be regulated pharmaceutically. In particular, four regulatory methods have been thoroughly studied; regulation of gene expression via microRNAs, regulation of AQP4 channel gating/trafficking via phosphorylation, regulation of water permeability using heavy metal ions, and regulation of water permeability using small molecule inhibitors. A major challenge when studying AQP4 regulation is inter-method variability. A compound or phosphorylation which shows an inhibitory effect in vitro may show no effect in a different in vitro method, or even show an increase in AQP4 expression in vivo. Although a large amount of variability exists between in vitro methods, some microRNAs, heavy metal ions, and two small molecule inhibitors, acetazolamide and TGN-020, have shown promise in the field of AQP4 regulation.
Topics: Acetazolamide; Animals; Aquaporin 4; Central Nervous System; Central Nervous System Diseases; Homeostasis; Humans; Ions; Metals; MicroRNAs; Niacinamide; Permeability; Phosphorylation; Potassium; Proteolipids; Thiadiazoles; Water
PubMed: 32111087
DOI: 10.3390/ijms21051603 -
Neurologic Clinics Feb 2017Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure of unknown cause occurring predominantly in young women of childbearing age.... (Review)
Review
Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure of unknown cause occurring predominantly in young women of childbearing age. The typical patient symptom profile is the presence of daily headache, pulse synchronous tinnitus, transient visual obscurations, and papilledema with its associated visual loss. Although surgical procedures are performed for those who fail medical therapy, their relative efficacy remains unclear. The main morbidity of IIH is from visual loss. This visual loss is present in most patients and can usually be reversed if recognized early in the patients' course and treated.
Topics: Acetazolamide; Diuretics; Humans; Papilledema; Pseudotumor Cerebri; Randomized Controlled Trials as Topic; Vision Disorders
PubMed: 27886895
DOI: 10.1016/j.ncl.2016.08.004 -
Respiratory Medicine Dec 2018After ascent to high altitude (≥2500 m), the inability of the human body to adapt to the hypobaric and hypoxia environment can induce tissue hypoxia, then a series... (Review)
Review
After ascent to high altitude (≥2500 m), the inability of the human body to adapt to the hypobaric and hypoxia environment can induce tissue hypoxia, then a series of high altitude illnesses including acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE) would develop. Symptoms of AMS include headache, dizziness, nausea, and vomiting; HAPE is characterized by orthopnea, breathlessness at rest, cough, pink frothy sputum, and results in obvious pulmonary edema that poses significant harm to people; HACE is characterized by ataxia and decreased consciousness, leading to coma and brain herniation which would be fatal if not treated promptly. This review article provides a current understanding of the pathophysiology of these three forms of high altitude illness and elaborates the current prevention and treatment measures of these diseases.
Topics: Acetazolamide; Acute Disease; Altitude Sickness; Calcium Channel Blockers; Carbonic Anhydrase Inhibitors; Cytokines; Dexamethasone; Endothelin-1; Hemodynamics; Humans; Hypertension, Pulmonary; Inflammation Mediators; Nifedipine; Nitric Oxide; Phosphodiesterase 5 Inhibitors; Pulmonary Alveoli; Sildenafil Citrate
PubMed: 30509704
DOI: 10.1016/j.rmed.2018.11.004 -
Chest Dec 2020Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Therapy options for OSA and central sleep apnea (CSA) are limited, thus many patients remain untreated. Clinically, acetazolamide is sometimes used for CSA; however, given overlapping pathophysiologic properties of OSA and CSA, we hypothesized that acetazolamide is equally effective for both types. Prior reviews focused on specific subtypes of sleep apnea, study designs, and languages, thus including few studies (typically ≤3) limiting insights.
RESEARCH QUESTION
How efficacious is acetazolamide for sleep apnea, and is its effect modified by sleep apnea type or acetazolamide dose?
STUDY DESIGN AND METHODS
We queried MEDLINE, EMBASE, and ClinicalTrials.gov from inception until March 11, 2019. Any study in which adults with OSA/CSA received oral acetazolamide vs no acetazolamide (control) that reported sleep apnea-related outcomes was eligible, independent of study design or language. Two reviewers independently assessed eligibility and abstracted data. Primary outcomes were apnea-hypopnea index (AHI) and oxygen saturation nadir. Quality of evidence (QoE) was rated with the use of Grades of Recommendation Assessment, Development and Evaluation methods.
RESULTS
We included 28 studies (13 OSA/15 CSA; N = 542; N = 553) that enabled meta-analyses for 24 outcomes. Acetazolamide doses ranged from 36 to 1000 mg/d and treatment duration from 1 to 90 d (median, 6 d). Overall, acetazolamide vs control lowered the AHI by -0.7 effect sizes (95% CI, -0.83 to -0.58; I = 0%; moderate QoE) that corresponded to a reduction of 37.7% (95% CI, -44.7 to -31.3) or 13.8/h (95% CI, -16.3 to -11.4; AHI = 36.5/h). The AHI reduction was similar in OSA vs CSA, but significantly greater with higher doses (at least up to 500 mg/d). Furthermore, acetazolamide improved oxygen saturation nadir by +4.4% (95% CI, 2.3 to 6.5; I = 63%; no evidence of effect modification; very low QoE) and several secondary outcomes that included sleep quality measures and BP (mostly low QoE).
INTERPRETATION
Short-term acetazolamide improved both OSA and CSA. Rigorous studies with long-term follow up are warranted to assess Acetazolamide's value for the chronic treatment of patients with sleep apnea.
CLINICAL TRIAL REGISTRATION
PROSPERO (CRD42019147504).
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Humans; Sleep Apnea, Central; Sleep Apnea, Obstructive; Treatment Outcome
PubMed: 32768459
DOI: 10.1016/j.chest.2020.06.078 -
ESC Heart Failure Dec 2022In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection... (Review)
Review
In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.
Topics: Humans; Acetazolamide; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Stroke Volume; Ventricular Function, Left
PubMed: 36546712
DOI: 10.1002/ehf2.14257 -
Journal of the American College of... May 2023Acetazolamide facilitates decongestion in acute decompensated heart failure (ADHF).
BACKGROUND
Acetazolamide facilitates decongestion in acute decompensated heart failure (ADHF).
OBJECTIVES
This study sought to investigate the effect of acetazolamide on natriuresis in ADHF and its relationship with outcomes.
METHODS
Patients from the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial with complete data on urine output and urine sodium concentration (UNa) were analyzed. Predictors of natriuresis and its relationship with the main trial endpoints were evaluated.
RESULTS
This analysis included 462 of 519 patients (89%) from the ADVOR trial. During 2 days after randomization, UNa was 92 ± 25 mmol/L on average, and total natriuresis was 425 ± 234 mmol. Allocation to acetazolamide strongly and independently predicted natriuresis with a 16 mmol/L (19%) increase in UNa and 115 mmol (32%) greater total natriuresis. Higher systolic blood pressure, better renal function, higher serum sodium levels, and male sex also independently predicted both a higher UNa and greater total natriuresis. A stronger natriuretic response was associated with faster and more complete relief of signs of volume overload, and this effect was already significant on the first morning of assessment (P = 0.022). A significant interaction was observed between the effect of allocation to acetazolamide and UNa on decongestion (P = 0.007). Stronger natriuresis with better decongestion translated into a shorter hospital stay (P < 0.001). After multivariable adjustments, every 10 mmol/L UNa increase was independently associated with a lower risk of all-cause death or heart failure readmission (HR: 0.92; 95% CI: 0.85-0.99).
CONCLUSIONS
Increased natriuresis is strongly related to successful decongestion with acetazolamide in ADHF. UNa may be an attractive measure of effective decongestion for future trials. (Acetazolamide in Decompensated Heart Failure with Volume Overload [ADVOR]; NCT03505788).
Topics: Humans; Male; Acetazolamide; Prospective Studies; Diuretics; Heart Failure; Water-Electrolyte Imbalance; Sodium
PubMed: 37197845
DOI: 10.1016/j.jacc.2023.03.400