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Neurologic disorders in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Robert Burger, Terry Rolan, David Lardizabal, Upinder Dhand, Aarti Sarwal, Pradeep Sahota
Women may present with raised intracranial pressure (idiopathic intracranial hypertension—IIH) during pregnancy. The risk is higher in obese women. The usual clinical manifestations are pressure like or dull, throbbing, generalized headache, blurred vision, or tinnitus. The optic disc margins may be blurred or frank papilledema may be present. Following an MRI brain, a lumbar puncture shows an opening pressure of 20 to 25cm or higher. Treatment consists of serial lumbar punctures or treatment with acetazolamide (500–2000mg a day). Acetazolamide may be used in the second half of pregnancy. Occasionally optic nerve sheath decompression may be necessary to help preserve vision (13).
Acetazolamide
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Acetazolamide is a sulfonamide derivative and non-competitive inhibitor of carbonic anhydrase with diuretic, antiglaucoma, and anticonvulsant properties. Acetazolamide is Indicated for the treatment of hypercapnia due to chronic obstructive pulmonary disease, idiopathic intracranial hypertension, prevention or treatment of postoperative intraocular pressure after cataract surgery, absence seizures and prophylaxis of acute mountain sickness (1, 2). In pharmaceutical products, acetazolamide is employed as acetazolamide sodium (CAS number 1424-27-7, EC number not available, molecular formula C4H5N4NaO3S2) (1).
Treatment of Chronic Fatigue Syndrome
Published in Jay A. Goldstein, Chronic Fatigue Syndromes, 2020
It is suggested that locus ceruleus inhibition of hippocampal activity produces anxiety. Benzodiazepines may reduce generalized anxiety but not sodium lactate induced panic. Since benzodiazepine receptors are dense in limbic structures, it may be that these anxiolytics act there but not in the brain stem. There are well-known pathways from the limbic system to the locus ceruleus. Gorman et al. suggest that “repeated stimulation of limbic neurons by brain stem discharge lowers the threshold to excitatory postsynaptic stimulation in the limbic lobe until `subpanic’ stimulation is capable of maintaining the ‘kindled’ anticipatory anxiety. Thus, even without the further occurrence of panic, the limbic area continues to have a reduced threshold for response to various stressors.” It may be that the hyperventilation that accompanies panic attacks causes reduced cerebral blood flow in the limbic system and is thereby responsible for the symptoms of hyperventilation syndrome. In our CFS SPECT scan population, the patients who chronically hyperventilated (as determined by end-tidal pCO2) could be symptomatically distinguished from those who did not only by the presence of fibromyalgia tender points. Addition of agents which markedly increase cerebral blood flow, such as calcium channel blockers (except for nimodipine) and acetazolamide, do not often reduce such symptoms. Patients with anxiety disorders, however, have normal, or increased, cerebral blood flow.89 Acetazolamide lowers brain pH but causes hyperventilation.
Quality of Life in Patients with Idiopathic Intracranial Hypertension and the Impact of the COVID-19 Pandemic
Published in Neuro-Ophthalmology, 2022
Neşe Çelebisoy, Ayşın Kısabay Ak, Hüseyin Nezih Özdemir, Figen Gökçay, Erhan Eser
Apart from the colour vision sub-scale of visual functioning, all other subscale scores of vision-targeted health status were significantly lower in the IIH patients compared with the healthy controls. Additionally, all other QOL scores including mental wellbeing assessed by the WHO-5; general, physical, psychological, social, and environmental aspects of QOL assessed by the EUROHIS-QOL 8-item index; and headache impact on daily living assessed by the HIT-6 scale were impaired in the IIH group. Similar results have been reported in previous studies. Kleinschmidt et al. found that patients with IIH had significantly lower scores for social functioning and had worse scores for both depression and anxiety.26 Daniels et al. found that NEI-VFQ-25 and SF-36 subscale scores were lower in IIH.21 Mulla et al. reported that headache was the main determinant of reduced QOL needing effective treatment.27 The IIH Treatment Trial demonstrated QOL reduction at disease onset with mild visual loss, linked with raised intracranial pressure.20 On the NEI-VFQ-25, ocular pain and distance driving subscale scores were prominently affected. Headache severity was associated with the NEI-VFQ-25 composite score, the Neuro-Ophthalmic Supplement score, and scores on SF-36. Visual loss, headache, neck pain, transient visual obscurations, and binocular diplopia were all independently associated with poorer QOL. Improvement was noted after treatment with acetazolamide at the 6 month follow-up visit.28
Contemporary management of the pseudotumor cerebri syndrome
Published in Expert Review of Neurotherapeutics, 2019
Carbonic anhydrase is a metalloenzyme which catalyzes the reversible hydration and dehydration of carbon dioxide and bicarbonate [23]. The human brain and choroid plexus contain many carbonic anhydrase isoforms. The secretion of CSF involves the transport of Na+, Cl- and HCO3- from the blood to the brain ventricles which is driven by an osmotic gradient [24]. Carbonic anhydrase inhibitors maintain pH and bicarbonate homeostasis and most of them incorporate a sulfonamide as a zinc binding group and act systemically, leading to off-target side effects (e.g. nausea, fatigue, depression). The inhibitory effect of acetazolamide on CSF secretion and flow was demonstrated in 1954 by Tschirigi et al. and confirmed in a cat model by Kister, who infused intravenous acetazolamide at various doses into cats and recorded CSF flow [25]. He found a decline in CSF flow to about 30% of control rates which occurred within 5 min, reached a maximum in 30 min and persisted for several hours, independent of the dose infused. Methazolamide is a lipophilic, methylated analogue of acetazolamide and an equally potent carbonic anhydrase inhibitor. Acetazolamide is more likely to cause metabolic acidosis, has greater urinary secretion and a longer duration of action in the proximal tubule than methazolamide [26]. The most common side effects of acetazolamide are paresthesias, weight loss, diarrhea, dyspepsia, nausea, and vomiting [20].
Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases
Published in Expert Opinion on Therapeutic Patents, 2018
Combination therapies of a CAI, preferentially topiramate 21, with other pharmacological agents, such as aldosterone derivative, or benzodiazepines, were claimed recently in two patents [55,56] as a therapeutic option for obstructive sleep apnea. The same effects were observed in a clinical study in which acetazolamide 1 was used alone or in combination with benzodiazepines for the treatment of the same condition [57]. However, the precise mechanism of action and the CAIs involved are unknown for the moment, but probably an improvement of the brain tissue oxygenation achieved after CA inhibition with some of these drugs (acetazolamide, topiramate, etc.) leads to the beneficial pharmacologic effect [58,59]. It is interesting to note that very recently it was possible to determine the rate of the CA – catalyzed reaction directly into the brain [60], which may have important consequences for understanding whether the activity of this important enzyme is different in patients with brain disorders compared to healthy individuals.