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- Topiramate-induced angle-closure glaucoma: cross-sensitivity with other sulphonamide derivatives causing anterior uveitis. [JOURNAL ARTICLE]
- Int Ophthalmol 2013 Jun 8.
Topiramate is a recognized cause of drug-induced acute angle-closure glaucoma. We describe a case presenting with bilateral acute angle-closure glaucoma caused by topiramate intake. Patient subsequently developed severe anterior uveitis caused by sulphonamide derivatives (acetazolamide and co-trimoxazole) due to cross-sensitivity, on two separate occasions. The present case also highlights the role of anterior segment optical tomography in diagnosis and follow-up. In a patient with known drug allergy to topiramate, other sulphonamide derivatives should be avoided to limit the ocular morbidity.
- Magnetic resonance imaging finding of empty sella in obesity related idiopathic intracranial hypertension is associated with enlarged sella turcica. [JOURNAL ARTICLE]
- Neuroradiology 2013 May 25.
INTRODUCTION:Empty sella in MRI is an important finding associated with idiopathic intracranial hypertension (IIH). This study assesses the sensitivity and reproducibility of several morphological measures of the sella and pituitary gland to indentify the measure that best differentiates IIH from controls. Additionally, the study assesses reversal in gland compression following treatment.
METHODS:Sagittal 3D-T1W sequence with 1 mm isotropic resolution was obtained from ten newly diagnosed IIH patients and 11 matched healthy controls. Follow-up MRI scans were obtained from eight patients at 1-week post-lumbar puncture and acetazolamide treatment. 1D and 2D measures of absolute and normalized heights and cross-sectional areas of the gland and sella were obtained to identify the measure that best differentiates IIH patients and controls.
RESULTS:Overall area-based measurements had higher sensitivity than length with p < 0.0001 for sella area compared with p = 0.004 for normalized gland height. The gland cross-sectional areas were similar in both cohorts (p = 0.557), while the sella area was significantly larger in IIH, 200 ± 24 versus 124 ± 25 mm(2), with the highest sensitivity and specificity, 100 % and 90.9 %, respectively. Absolute gland area was the most sensitive measure for assessing post treatment changes, with 100 % sensitivity and 50 % specificity. Average post-treatment gland area was 18 % larger (p = 0.016). Yet, all eight patients remained within the empty sella range based on a normalized gland area threshold of 0.41.
CONCLUSIONS:Sellar area is larger in IIH, and it demonstrated highest sensitivity for differentiating IIH from control subjects, while absolute gland area was more sensitive for detecting post treatment changes.
- Acetazolamide for high intracranial pressure cerebrospinal fluid leaks. [JOURNAL ARTICLE]
- Int Forum Allergy Rhinol 2013 Jun 3.
BACKGROUND:Acetazolamide has become a standard treatment for cerebrospinal fluid (CSF) leaks associated with intracranial hypertension. The purpose of the current study was to evaluate the effectiveness of acetazolamide at decreasing elevated CSF pressure in this patient population.
METHODS:Prospective evaluation and data collection of high intracranial pressure CSF leaks was performed. Subjects underwent CSF diversion and postoperative assessment of pressure changes via a standard protocol. Lumbar drains or ventriculostomies were clamped on postoperative day 2 for 4 hours prior to assessment with a manometer. Acetazolamide (500 mg) was administered orally immediately following the recording and CSF pressure was measured after 4 hours. Data regarding demographics, etiology of CSF leak, body mass index (BMI), location and size of defect, and clinical follow-up were also collected.
RESULTS:Thirty-six patients (average age 50 years) with 42 CSF leaks (39 spontaneous, 3 traumatic) and an average BMI of 36.1 were evaluated. Success rate of primary repair was 94.4%, but all patients were effectively sealed with subsequent endoscopic reconstruction (average 80 weeks follow-up). Intracranial pressure (cm H2 O) via lumbar puncture or ventriculostomy (n = 2) after clamping was 32.0 ± 7.4. Administration of acetazolamide significantly decreased intracranial pressure to 21.9 ± 7.5 in the 4-6 hour time frame studied (p < 0.0001).
CONCLUSION:This study provides some of the first direct evidence of decreased intracranial pressure associated with the oral administration of acetazolamide. In combination with the excellent endoscopic repair outcomes noted in a high risk population, this evidence supports the routine use of acetazolamide in patients with high intracranial pressure CSF leaks.
- [Sixth, seventh and tenth cranial nerve palsies associated with pseudotumor cerebri in a 13-year-old boy.] [JOURNAL ARTICLE]
- J Fr Ophtalmol 2013 May 31.
We describe the case of a 13-year-old boy who presented to the emergency department with an acute onset paresis of the left abducens, facial and vagus nerves. Bilateral papilledema was seen on fundoscopy. Blood tests and brain magnetic resonance imaging and angiography showed no abnormalities. A lumbar puncture revealed an elevated intracranial pressure (575mmH2O) and clear cerebrospinal fluid. The diagnosis of pseudotumor cerebri (PTC) associated with multiple cranial nerve palsies was made. Treatment with acetazolamide was initiated, resulting in progressive improvement with no sequelae and no clinical recurrence over an 8-month follow-up period. PTC in children can present with a wide spectrum of neurological signs, especially cranial nerve palsies which are most likely related to a pressure-dependent stretching mechanism. In 2007, distinctive diagnostic criteria for pediatric PTC were established, including the presence of any cranial nerve palsy in the absence of an identifiable etiology.
- Drug therapy for obstructive sleep apnoea in adults. [Journal Article, Research Support, Non-U.S. Gov't]
- Cochrane Database Syst Rev 2013.:CD003002.
The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) applied via a mask during sleep. However, this is not tolerated by all individuals and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of rapid eye movement (REM) sleep, an increase in cholinergic tone during sleep, an increase in arousal threshold, a reduction in airway resistance and a reduction in surface tension in the upper airway.To determine the efficacy of drug therapies in the specific treatment of sleep apnoea.We searched the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2012.Randomised, placebo controlled trials involving adult patients with confirmed OSA. We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. We excluded studies investigating treatment of associated conditions such as excessive sleepiness, hypertension, gastro-oesophageal reflux disease and obesity.We used standard methodological procedures recommended by The Cochrane Collaboration.Thirty trials of 25 drugs, involving 516 participants, contributed data to the review. Drugs had several different proposed modes of action and the results were grouped accordingly in the review. Each of the studies stated that the participants had OSA but diagnostic criteria were not always explicit and it was possible that some patients with central apnoeas may have been recruited.Acetazolamide, eszopiclone, naltrexone, nasal lubricant (phosphocholinamine) and physiostigmine were administered for one to two nights only. Donepezil in patients with and without Alzheimer's disease, fluticasone in patients with allergic rhinitis, combinations of ondansetrone and fluoxetine and paroxetine were trials of one to three months duration, however most of the studies were small and had methodological limitations. The overall quality of the available evidence was low.The primary outcomes for the systematic review were the apnoea hypopnoea index (AHI) and the level of sleepiness associated with OSA, estimated by the Epworth Sleepiness Scale (ESS). AHI was reported in 25 studies and of these 10 showed statistically significant reductions in AHI.Fluticasone in patients with allergic rhinitis was well tolerated and reduced the severity of sleep apnoea compared with placebo (AHI 23.3 versus 30.3; P < 0.05) and improved subjective daytime alertness. Excessive sleepiness was reported to be altered in four studies, however the only clinically and statistically significant change in ESS of -2.9 (SD 2.9; P = 0.04) along with a small but statistically significant reduction in AHI of -9.4 (SD 17.2; P = 0.03) was seen in patients without Alzheimer's disease receiving donepezil for one month. In 23 patients with mild to moderate Alzheimer's disease donepezil led to a significant reduction in AHI (donepezil 20 (SD 15) to 9.9 (SD 11.5) versus placebo 23.2 (SD 26.4) to 22.9 (SD 28.8); P = 0.035) after three months of treatment but no reduction in sleepiness was reported. High dose combined treatment with ondansetron 24 mg and fluoxetine 10 mg showed a 40.5% decrease in AHI from the baseline at treatment day 28. Paroxetine was shown to reduce AHI compared to placebo (-6.10 events/hour; 95% CI -11.00 to -1.20) but failed to improve daytime symptoms.Promising results from the preliminary mirtazapine study failed to be reproduced in the two more recent multicentre trials and, moreover, the use of mirtazapine was associated with significant weight gain and sleepiness. Few data were presented on the long-term tolerability of any of the compounds used.There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short-term outcomes. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24% and 45%. For donepezil and fluticasone, studies of longer duration with a larger population and better matching of groups are required to establish whether the change in AHI and impact on daytime symptoms are reproducible. Individual patients had more complete responses to particular drugs. It is possible that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.
- Nrf2 activation: A potential strategy for the prevention of acute mountain sickness. [JOURNAL ARTICLE]
- Free Radic Biol Med 2013 May 27.
Reactive oxygen species (ROS) formed during acute high altitude exposure contribute to cerebral vascular leak and development of acute mountain sickness (AMS). Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) is a transcription factor that regulates expression of greater than 90% of antioxidant genes, but prophylactic treatment with Nrf2 activators has not yet been tested as an AMS therapy. We hypothesized that prophylactic activation of the antioxidant genome with Nrf2 activators would attenuate high-altitude-induced ROS formation and cerebral vascular leak and that some drugs currently used to treat AMS symptoms have an additional trait of Nrf2 activation. Drugs commonly used to treat AMS were screened with a luciferase reporter cell system for their effectiveness to activate Nrf2, as well as being tested for their ability to decrease high altitude cerebral vascular leak in vivo. Compounds that showed favorable results for Nrf2 activation from our screen and attenuated high altitude cerebral vascular leak in vivo were further tested in brain microvascular endothelial cells (BMECs) to determine if they attenuated hypoxia-induced ROS production and monolayer permeability. Of nine drugs tested, with the exception of dexamethasone, only drugs that showed the ability to activate Nrf2 (Protandim, methazolamide, nifedipine, amlodipine, ambrisentan, and sitaxentan) decreased high-altitude-induced cerebral vascular leak in vivo. In vitro, Nrf2 activation in BMECs before 24h hypoxia exposure attenuated hypoxic-induced hydrogen peroxide production and permeability. Prophylactic Nrf2 activation is effective at reducing brain vascular leak from acute high altitude exposures. Compared to acetazolamide, methazolamide may offer better protection against AMS. Nifedipine, in addition to its known vasodilatory activities in the lung and protection against high altitude pulmonary edema, may provide protection against brain vascular leak as well.
- Breathing and sleep at high altitude. [JOURNAL ARTICLE]
- Respir Physiol Neurobiol 2013 May 28.
We provide an updated review on the current understanding of breathing and sleep at high altitude in humans. We conclude that: (1) progressive changes in pH initiated by the respiratory alkalosis do not underlie early (<48h) ventilatory acclimatization to hypoxia (VAH) because this still proceeds in the absence of such alkalosis; (2) for VAH of longer duration (>48h), complex cellular and neurochemical re-organization occurs both in the peripheral chemoreceptors as well as within the central nervous system. The latter is likely influenced by central acid-base changes secondary to the extent of the initial respiratory responses to initial exposure to high altitude; (3) sleep at high altitude is disturbed by various factors, but principally by periodic breathing; (4) the extent of periodic breathing during sleep at altitude intensifies with duration and severity of exposure; (5) complex interactions between hypoxic-induced enhancement in peripheral and central chemoreflexes and cerebral blood flow - leading to higher loop gain and breathing instability - underpin this development of periodic breathing during sleep; (6) because periodic breathing may elevate rather than reduce mean SaO2 during sleep, this may represent an adaptive rather than maladaptive response; (7) although oral acetazolamide is an effective means to reduce periodic breathing by 50-80%, recent studies using positive airway pressure devices to increase dead space, hyponotics and theophylline are emerging but appear less practical and effective compared to acetazolamide. Finally, we suggest avenues for future research, and discuss implications for understanding sleep pathology.
- Drug use in primary open angle glaucoma: A prospective study at a tertiary care teaching hospital. [Journal Article]
- Indian J Pharmacol 2013 Mar; 45(2):117-20.
To study drug use pattern in patients of primary open angle glaucoma (POAG) and to analyze the cost of different anti-glaucoma medications.This prospective study was carried in the glaucoma clinic of a tertiary care teaching hospital over a period of 9 months. The data collected for patients with POAG included the patient's demographic details and the drugs prescribed. Data were analyzed for drug use pattern and cost drugs used.In a total 180 prescriptions (297 drugs) analyzed, most drugs (83.83%) were prescribed by topical route as eye drops. β blockers (93.88%) were found to be the most frequently prescribed for POAG. Timolol (82.22%) was the most frequently prescribed drug and timolol with acetazolamide (17.22%) was the most commonly prescribed drug combination. Fixed dose combinations constituted 26.66% of prescriptions. β blockers were found to be cheaper than other anti-glaucoma drugs while prostaglandins analogs were the costliest. Instructions about the route, frequency and duration of treatment were present in all prescriptions. However, instructions regarding instillation of eye drops were missing in all prescriptions.
- A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease. [Journal Article]
- Neurology 2013 May 28; 80(22):2081.
Editors' Note: In this week's WriteClick, Dr. Shang and authors Silvestrini et al. discuss the role of transcranial Doppler (TCD)-measured vasomotor reserve (VMR) in studying carotid stenosis and cerebral microcirculation. VMR evaluates the compensatory response of the cerebral small vessels (autoregulation) to a stimulus. Carbon dioxide or acetazolamide is used to stimulate vasodilation and then VMR is calculated from the measured change in blood velocity. Vessels already dilated from decreased perfusion pressure due to carotid stenosis have less capacity to react. VMR has been used to analyze syncope, predict autonomic dysfunction in Parkinson disease, and study circulation and autoregulation in migraine with aura, Alzheimer disease, and even altitude sickness.