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Cureus Feb 2024Idiopathic intracranial hypertension (IIH) and multiple sclerosis (MS) are rare neurological disorders that largely affect females within the reproductive age group....
Idiopathic intracranial hypertension (IIH) and multiple sclerosis (MS) are rare neurological disorders that largely affect females within the reproductive age group. The clinical pictures of both diseases can overlap, which therefore places great importance on accurately studying and reporting their concurrence. Therein, we report a case of IIH presenting and progressing simultaneously with MS. This young, previously healthy female presented with the primary complaint of a severe right-sided headache associated with blurred vision and a finding of papilledema. The initial investigations including a lumbar puncture (LP) that revealed high opening pressure (more than 25 mm HO) with normal cerebrospinal fluid (CSF) analysis led to an impression of idiopathic intracranial hypertension, and she was treated accordingly with acetazolamide and scheduled for regular follow-ups with both neurology and neuro-ophthalmology. However, about two months after the initial presentation, she complained of unusual headaches, and a neuro-ophthalmology clinical evaluation revealed complete right homonymous hemianopia, suggesting a lesion in the left temporo-parietal occipital region. The patient was thus admitted as a case of cerebral edema following an urgent brain magnetic resonance imaging (MRI). After obtaining thorough imaging and workup, the patient was given steroids and markedly improved, favoring a diagnosis of tumefactive MS with IIH.
PubMed: 38314385
DOI: 10.7759/cureus.53374 -
Cureus Sep 2023In this case report, a patient with neuroretinitis from a infection is described, and insights into methods to distinguish this type of case from more common...
In this case report, a patient with neuroretinitis from a infection is described, and insights into methods to distinguish this type of case from more common etiologies of optic nerve edema are presented. A 21-year-old female with a history of right monocular vision loss due to amblyopia presented to the emergency department (ED) with occipital headache, fever, dizziness, nasal congestion, and painless blurry vision in the left eye for one day. A lumbar puncture found a slightly high opening pressure but no evidence of meningitis. The patient was diagnosed with a viral illness and discharged with outpatient follow-up. The patient, however, had persistent central vision loss and recurring headaches and returned to the ED. Subsequent ultrasound of the patient's optic nerve revealed significant optic nerve swelling. A new working diagnosis of idiopathic intracranial hypertension was made, and the patient was started on oral acetazolamide. On the next day, she was seen by ophthalmology, and recent scratches from her cat were noted on her arm. She tested positive for and was started on doxycycline and rifampin. Nearly two weeks after the initial presentation, a macular star pattern, indicative of neuroretinitis, was noted on the fundoscopic exam. The patient had recovered her vision by three months later. In ED cases with unilateral vision loss, early use of point-of-care ultrasound and infection with should always be considered. Early serology testing may be warranted to allow for earlier treatment since classic signs of neuroretinitis may not be apparent at the onset.
PubMed: 37885521
DOI: 10.7759/cureus.45866 -
Endocrinology, Diabetes & Metabolism... Oct 2023A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around...
SUMMARY
A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around the left shoulder and the right hip joint. The patient could not fully extend her fingers because of skin sclerosis in both hands. Laboratory studies showed hyperphosphataemia and a high ratio of renal tubular maximum reabsorption of phosphate to glomerular filtration rate. There were no abnormalities in serum calcium, creatinine, alkaline phosphatase, and intact parathyroid hormone levels, whereas serum fibroblast growth factor 23 was low. Hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome (HFTC/HHS) was diagnosed using whole genome sequencing that revealed a novel frameshift beyond the 584th threonine located in the lectin domain of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 associated with a duplication of the 1748th thymine in the coding region of the corresponding gene. Furthermore, anti-nuclear, anti-centromere, and anti-cardiolipin antibodies were positive, implying that comorbid limited type scleroderma might play a role in tumoural calcinosis (TC) development. A low phosphate diet was prescribed with phosphate-lowering medications, including aluminium hydroxide, acetazolamide, and sevelamer hydrochloride. The patient displayed a decrease in serum phosphate levels from 6.5 to 5.5 mg/dL 10 months after the initiation of treatment, but her TC had not improved during treatment for more than 1 year. This case was interesting because the patient with HFTC/HHS exhibited TC despite being over her 60s, and subsequent scleroderma might contribute to the specific clinical course. When HFTC/HHS presents with elderly-onset TC, the involvement of comorbidities in exacerbating TC should be considered.
LEARNING POINTS
HFTC/HHS occurs on an autosomal recessive basis, but its clinical course and manifestations differ significantly throughout the cases. HFTC/HHS may be undiagnosed until later in life because of its rarity, unfamiliarity, and phenotype diversity; therefore, HFTC/HHS should be included in the differential diagnosis of elderly patients with unexplained hyperphosphataemia or ectopic calcinosis. Comorbidities, including rheumatologic disorders, may contribute to developing HFTC/HHS-associated calcinosis.
PubMed: 37787752
DOI: 10.1530/EDM-23-0071 -
Journal of Clinical Medicine Jun 2024This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve...
This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve decongestion in the context of patients hospitalized for acute heart failure (HF). However, data in terms of safety are lacking. We conducted a monocentric observational prospective study from November 2023 to February 2024 in a 12-bed cardiology department, recording adverse events (hypotension, severe metabolic acidosis, severe hypokalemia and renal events) during in-hospital HF treatment. All patients hospitalized for acute HF during the study period treated with ACZ (500 mg IV daily for 3 days) on top of IV furosemide ( = 28, 48.3%) were compared with patients who have been treated with IV furosemide alone ( = 30, 51.7%). The patients treated with ACZ were younger than those without (median age 78 (range 67-86) vs. 85 (79-90) years, respectively, = 0.01) and had less frequent chronic kidney disease (median estimated glomerular fraction rate (60 (35-65) vs. 38 (26-63) mL/min, = 0.02). As concerned adverse events during HF treatment, there were no differences in the occurrences of hypotension (three patients [10.7%] in the ACZ group vs. four [13.3%], = 0.8), renal events (four patients [14.3%] in the ACZ group vs. five [16.7%], = 1) and severe hypokalemia (two [7.1%] in the ACZ group vs. three [10%], = 1). No severe metabolic acidosis occurred in either group. Although the clinical characteristics differed at baseline, with younger age and better renal function in patients receiving ACZ, the tolerance profile did not significantly differ from patients receiving furosemide alone. Additional observational data are needed to further assess the safety of ACZ-furosemide combination in the in-hospital management of HF, especially in older, frail populations.
PubMed: 38929950
DOI: 10.3390/jcm13123421 -
Microbiology Spectrum Aug 2023Enterococcus faecalis is a hospital-associated opportunistic pathogen that can cause infections with high mortality, such as infective endocarditis. With an increasing...
Enterococcus faecalis is a hospital-associated opportunistic pathogen that can cause infections with high mortality, such as infective endocarditis. With an increasing occurrence of multidrug-resistant enterococci, there is a need for alternative strategies to treat enterococcal infections. We isolated a gentamicin-hypersusceptible E. faecalis strain from a patient with infective endocarditis that carried a mutation in the alpha-carbonic anhydrase (α-CA) and investigated how disruption of α-CA sensitized E. faecalis to killing with gentamicin. The gentamicin-hypersusceptible α-CA mutant strain showed increased intracellular gentamicin uptake in comparison to an isogenic strain encoding full-length, wild-type α-CA. We hypothesized that increased gentamicin uptake could be due to increased proton motive force (PMF), increased membrane permeability, or both. We observed increased intracellular ATP production in the α-CA mutant strain, suggesting increased PMF-driven gentamicin uptake contributed to the strain's gentamicin susceptibility. We also analyzed the membrane permeability and fatty acid composition of isogenic wild-type and α-CA mutant strains and found that the mutant displayed a membrane composition that was consistent with increased membrane permeability. Finally, we observed that exposure to the FDA-approved α-CA inhibitor acetazolamide lowered the gentamicin MIC of eight genetically diverse E. faecalis strains with intact α-CA but did not change the MIC of the α-CA mutant strain. These results suggest that α-CA mutation or inhibition increases PMF and alters membrane permeability, leading to increased uptake of gentamicin into E. faecalis. This connection could be exploited clinically to provide new combination therapies for patients with enterococcal infections. Enterococcal infections can be difficult to treat, and new therapeutic approaches are needed. In studying an E. faecalis clinical strain from an infected patient, we found that the bacteria were rendered hypersusceptible to aminoglycoside antibiotics through a mutation that disrupted the α-CA. Our follow-on work suggested two different ways that α-CA disruption causes increased gentamicin accumulation in E. faecalis: increased proton motive force-powered uptake and increased membrane permeability. We also found that a mammalian CA inhibitor could sensitize a variety of E. faecalis strains to killing with gentamicin. Given that mammalian CA inhibitors are frequently used to treat conditions such as glaucoma, hypertension, and epilepsy, our findings suggest that these "off-the-shelf" inhibitors could also be useful partner antibiotics for the treatment of E. faecalis infections.
Topics: Animals; Humans; Enterococcus; Carbonic Anhydrases; Microbial Sensitivity Tests; Anti-Bacterial Agents; Gentamicins; Endocarditis, Bacterial; Gram-Positive Bacterial Infections; Mammals
PubMed: 37260400
DOI: 10.1128/spectrum.03963-22 -
Cureus Aug 2023Sarcoidosis is an immune-mediated disease that can involve multiple systems. Sarcoidosis of the nervous system or neurosarcoidosis may present as cranial mononeuropathy,...
Sarcoidosis is an immune-mediated disease that can involve multiple systems. Sarcoidosis of the nervous system or neurosarcoidosis may present as cranial mononeuropathy, hypothalamic involvement, aseptic meningitis, granulomatous inflammation in the brain parenchyma or spinal cord, peripheral neuropathy, and, in rare cases, as myopathy and benign intracranial hypertension. The most common cranial nerve involvement is the facial nerve, which can present as unilateral or bilateral facial nerve palsy, often with recurrent episodes. Involvement of other cranial nerves such as the second and eighth cranial nerves has also been reported. Granulomatous inflammation in the spinal cord presents as myelopathy or radiculopathy. Peripheral neuropathy can manifest as mononeuropathy, mononeuritis multiplex, or generalized sensory-motor neuropathy. Carpal tunnel syndrome is more common in patients with sarcoidosis compared to the general population. Here, we describe the case of a 40-year-old female who presented with heaviness of the head and blurred vision, with a prior history of left-sided Bell's palsy. Bilateral papilledema was observed during the fundus examination. MRI of the brain revealed signs suggestive of benign intracranial hypertension. The cerebrospinal fluid (CSF) opening pressure was measured at 40 cmH2O. Biopsy of bilateral hilar lymphadenopathy indicated granulomatous inflammation consistent with sarcoidosis. The patient was started on steroids and acetazolamide, and she had a dramatic improvement in symptoms.
PubMed: 37701004
DOI: 10.7759/cureus.43363 -
International Journal of Molecular... Apr 2024In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is...
In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca entry triggers a transepithelial Ca flux to regulate proximal tubular (PT) luminal [Ca], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca entry compared to the WT counterparts because of significant inhibition by the store-operated Ca entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca entry) inhibitors (Pyr10), Ca entry by WTT cells was moderately inhibited, suggesting that the Ca and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.
Topics: Animals; Hypercalciuria; Hydrogen-Ion Concentration; Mice; Mice, Knockout; Calcium Oxalate; Kidney Calculi; Calcium Phosphates; Nephrolithiasis; Calcium; TRPC Cation Channels; Kidney Tubules, Proximal; Male; Disease Models, Animal; Mice, Inbred C57BL; Acetazolamide
PubMed: 38732005
DOI: 10.3390/ijms25094787 -
Journal of the American Board of Family... 2024Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure..
Consider IV Acetazolamide in addition to standard IV loop diuretic therapy in patients hospitalized for acute decompensated heart failure..
Topics: Humans; Acetazolamide; Heart Failure; Acute Disease; Sodium Potassium Chloride Symporter Inhibitors; Diuretics; Carbonic Anhydrase Inhibitors
PubMed: 38740482
DOI: 10.3122/jabfm.2023.230379R0 -
Wiener Klinische Wochenschrift Jan 2024Idiopathic intracranial hypertension (IIH) is becoming increasingly more prevalent bearing the risk of visual impairment and affecting the quality of life. Clinical...
BACKGROUND
Idiopathic intracranial hypertension (IIH) is becoming increasingly more prevalent bearing the risk of visual impairment and affecting the quality of life. Clinical presentation and outcome are heterogeneous. Large, well-characterized cohorts are scarce.
OBJECTIVE
To characterize the clinical spectrum, diagnostic findings, therapeutic management, and outcome of IIH.
METHODS
We identified patients with IIH according to modified Friedman criteria treated at our center between 2014 and 2021. The Vienna IIH database is described in detail.
RESULTS
Of 113 patients 89% were female (mean age 32.3 years). Median body mass index (BMI) was 31.8, with 85% overweight (BMI > 25) and 5% were classified as IIH without papilledema. Headache was present in 84% and showed migraine features in 43%. Median opening pressure in lumbar puncture was 31 cmHO. Pharmacotherapy (predominantly acetazolamide) was established in 99%, 56% required at least 1 therapeutic lumbar puncture and 13% a surgical intervention. After a median 3.7 years follow-up, 57% had achieved significant weight loss, papilledema was present in 59% and headache in 76% (58% improved). Comparing initial presentation to follow-up, perimetry was abnormal in 67% vs. 50% (8% worsened, 24% improved) and transorbital sonography in 87% vs. 65% with a median optic nerve sheath diameter of 5.4 mm vs. 4.9 mm. Median peripapillary retinal nerve fiber layer thickness decreased from 199 µm to 99 µm and ganglion cell layer volume from 1.13 mm to 1.05 mm.
CONCLUSION
The large representative Vienna IIH cohort characterizes IIH-related symptoms, diagnostic findings, treatment, and outcome emphasizing substantial long-term sequelae of IIH. Future analyses will aim to refine phenotyping and identify factors predicting outcome.
Topics: Humans; Female; Adult; Male; Pseudotumor Cerebri; Papilledema; Austria; Quality of Life; Headache
PubMed: 37650963
DOI: 10.1007/s00508-023-02252-x -
Neuro-oncology Advances 2024A significant unmet need exists for the treatment of glioblastoma, wildtype (GBM). Preclinical work shows that acetazolamide sensitizes GBM to temozolomide (TMZ) by...
BACKGROUND
A significant unmet need exists for the treatment of glioblastoma, wildtype (GBM). Preclinical work shows that acetazolamide sensitizes GBM to temozolomide (TMZ) by overcoming TMZ resistance due to BCL-3-dependent upregulation of carbonic anhydrase. Acetazolamide is Food and Drug Administration-approved for the treatment of altitude sickness. Drug repurposing enables the application of drugs to diseases beyond initial indications. This multi-institutional, open-label, phase I trial examined a combination of acetazolamide and TMZ in patients with promoter-methylated high-grade glioma.
METHODS
A total of 24 patients (GBM, -wildtype = 22; Grade 4 astrocytoma, -mutant = 1; Grade 3 astrocytoma, -mutant = 1) were accrued over 17 months. All patients received oral acetazolamide (250 mg BID for 7 days increased to 500 mg BID for Days 8-21 of each 28-day cycle) during the adjuvant phase of TMZ for up to 6 cycles.
RESULTS
No patient had a dose-limiting toxicity. Adverse events were consistent with known sequelae of acetazolamide and TMZ. In the 23 WHO Grade 4 patients, the median overall survival (OS) was 30.1 months and the median progression-free survival was 16.0 months. The 2-year OS was 60.9%. In total 37% of the study population had high BCL-3 staining and trended toward shorter OS (17.2 months vs N.R., = .06).
CONCLUSIONS
The addition of acetazolamide is safe and tolerable in GBM patients receiving standard TMZ. Survival results compare favorably to historical data from randomized trials in patients with promotermethylated GBM and support examination of acetazolamide in a randomized trial. BCL-3 expression is a potential biomarker for prognosis in GBM or for patients more likely to benefit from TMZ.
PubMed: 38420615
DOI: 10.1093/noajnl/vdae014