Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH

Alperin, Noam; Oliu, Carlos J.; Bagci, Ahmet; Lee, Sang H.; Kovanlıkaya, İlhami; Adams, David J.; Katzen, Heather; Ivkovic, M.; Heier, Linda; Relkin, Norman

doi:10.1212/wnl.0000000000000313

Cited by 61 publications

(53 citation statements)

References 15 publications

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“…40 In addition, a recent study reported that low-dose acetazolamide, which is frequently used to treat cerebral edema, can also reduce PVL in idiopathic normal pressure hydrocephalus. 1 Notably, patients with severe ventriculomegaly were more responsive to acetazolamide compared with the patients with moderate ventriculomegaly. The results of the present study indicate that the pore pressure around the ventricular horns becomes positive in severely enlarged ventricles, thus enhancing the drainage of PVL by acetazolamide.…”

Section: Influence Of Geometrical Characteristics Of the Hydrocephalimentioning

confidence: 98%

Finite element analysis of periventricular lucency in hydrocephalus: extravasation or transependymal CSF absorption?

Kim¹,

Jeong

Park³

et al. 2016

JNS

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P eriventricular lucency (PVL) refers to the decreased attenuation level, or "blurring," around the periventricular area on CT, or T2 hyperintensity on MRI. This radiological phenomenon is a common finding not only in various neurological or cardiovascular disorders, but also in the general elderly population. 21,22,29,47 Although widely researched and documented, the pathogenesis and clinical significance of PVL are still inconclusive, especially for PVL associated with hydrocephalus. Hydrocephalus is defined as the excessive accumulation of CSF in the brain due to various causes. The disease is considered to be caused by an imbalance between the formation and reabsorption of CSF, due to the disturbance in CSF dynamics. 28 Considering the site of the obstruction in the flow of CSF, two types of hydrocephalus have been defined: communicating and noncommunicating. PVL in hydrocephalus was first documented by Naidich et al. 27PVL and enlarged ventricles are typical radiological signs of acute or noncommunicating hydrocephalus.30 However, these two signs also exist in chronic or communicating hydrocephalus, although the prevalence is relatively lower. 25,34 In either case, the pathogenesis of PVL remains abbreviatioNs FE = finite element; ICP = intracranial pressure; ISF = interstitial fluid; PVL = periventricular lucency; TPG = transmantle pressure gradient. obJective Periventricular lucency (PVL) is often observed in the hydrocephalic brain on CT or MRI. Earlier studies have proposed the extravasation of ventricular CSF into the periventricular white matter or transependymal CSF absorption as possible causes of PVL in hydrocephalus. However, there is insufficient evidence for either theory to be conclusive. methods A finite element (FE) model of the hydrocephalic brain with detailed anatomical geometry was constructed to investigate the possible mechanism of PVL in hydrocephalus. The initiation of hydrocephalus was modeled by applying a transmantle pressure gradient (TPG). The model was exposed to varying TPGs to investigate the effects of different geometrical characteristics on the distribution of PVL. The edema map was derived based on the interstitial pore pressure. results The model simulated the main radiological features of hydrocephalus, i.e., ventriculomegaly and PVL. The degree of PVL, assessed by the pore pressure, was prominent in mild to moderate ventriculomegaly. As the degree of ventriculomegaly exceeded certain values, the pore pressure across the cerebrum became positive, thus inducing the disappearance of PVL. coNclusioNs The results are in accordance with common clinical findings of PVL. The degree of ventriculomegaly significantly influences the development of PVL, but two factors were not linearly correlated. The results are indicative of the transependymal CSF absorption as a possible cause of PVL, but the extravasation theory cannot be formally rejected.

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Section: Influence Of Geometrical Characteristics Of the Hydrocephalimentioning

confidence: 98%

Finite element analysis of periventricular lucency in hydrocephalus: extravasation or transependymal CSF absorption?

Kim¹,

Jeong

Park³

et al. 2016

JNS

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“…In humans with idiopathic normal-pressure hydrocephalus, low-dose acetazolamide has been associated with a reduction in periventricular white matter hyperintensities Congenital Hydrocephalus seen on MRI. 13 Furosemide is a loop diuretic that acts mainly by inhibiting sodium reabsorption in the nephron at the thick ascending limb of the loop of Henle. 14 Furosemide has also been shown to decrease CSF production and intracranial pressure in rabbits.…”

Section: Medical Treatmentmentioning

confidence: 99%

Congenital Hydrocephalus

Estey¹

2016

Veterinary Clinics of North America: Small Animal Practice

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There are several types of hydrocephalus, which are characterized based on the location of the cerebrospinal fluid (CSF) accumulation. Physical features of animals with congenital hydrocephalus may include a dome-shaped skull, persistent fontanelle, and bilateral ventrolateral strabismus. Medical therapy involves decreasing the production of CSF. The most common surgical treatment is placement of a ventriculoperitoneal shunt. Postoperative complications may include infection, blockage, drainage abnormalities, and mechanical failure.

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“…CAIs are also currently approved for the prevention of acute mountain sickness and related cerebral edema and as diuretics. Furthermore, ATZ is used in the treatment for idiopathic intracranial hypertension and normal pressure hydrocephalus (Alperin et al., 2014). Their use in these neurological disorders as well as in epilepsy (Aggarwal et al., 2013) confirms the ability of these drugs to reach the brain at effective concentrations.…”

Section: Introductionmentioning

confidence: 99%

Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity

et al. 2018

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SummaryMounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer's disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)‐mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than MTZ. Both MTZ and ATZ prevented mitochondrial membrane depolarization and H2O2 generation, with no effects on intracellular pH or ATP production. Importantly, the drugs did not primarily affect calcium homeostasis. This work suggests a new role for carbonic anhydrases (CAs) in the Aβ‐induced mitochondrial toxicity associated with AD and cerebral amyloid angiopathy (CAA), and paves the way to AD clinical trials for CAIs, FDA‐approved drugs with a well‐known profile of brain delivery.

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Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH

Cited by 61 publications

References 15 publications

Finite element analysis of periventricular lucency in hydrocephalus: extravasation or transependymal CSF absorption?

Finite element analysis of periventricular lucency in hydrocephalus: extravasation or transependymal CSF absorption?

Congenital Hydrocephalus

Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity

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