2.2.2. Mannitol

electrolytes is suggested during acetazolamide treatment, and potassium and bicarbonate

In expert opinion, acetazolamide is the most suitable drug alone or in combination with

Furosemide selectively inhibits sodium reabsorption in the nephron at the loop of Henle, which is a potent loop diuretic used to treat high blood pressure, congestive heart failure, and swelling due to excess body water and also used in hyperkalemia and acute renal failure [1, 10]. Studies have shown that furosemide reduces the production of cerebrospinal fluid by inhibiting the transport of Cl to the cerebrospinal fluid [21–24]. In the medical treatment of hydrocephaly, the usual dose of furosemide is 1 mg/kg/day divided into two doses/day [25, 26]. Adverse effects of furosemide therapy are serum electrolyte disturbances, hypotension, and ototoxicity; for this

Studies have shown that combination therapy of furosemide and acetazolamide was not effective in decreasing the frequency of shunting or death. Therefore, this therapy is not

The proximal tubule and descending limb of Henle's loop are freely permeable to water. Osmotic diuretic agents are freely filtered at the glomerulus, undergo minimal reabsorption by the renal tubules causes water to be retained in these segments and promotes water diuresis. Four osmotic diuretics are available: glycerin, isosorbide, mannitol, and urea; mannitol is the most commonly used in clinical practice and the most extensively studied. Osmotic diuretics are used to increase water excretion and to promote prompt removal of renal toxins

Isosorbide (1,4:3,6-dianhydro-d-glucitol) is an osmotic agent developed for the treatment of glaucoma. It has also been shown to reduce the intracranial pressure [31, 32]. The single oral dose of isosorbide significantly reduces intraventricular pressure. Multiple studies showed the

Lorber et al. have studied the use of isosorbide in patients with various types of hydrocephaly; they reported that patient did not require shunt insertions after prolonged medication with isosorbide. But isosorbide did not replace than surgery and was less efficient than surgery

Lorber concluded that isosorbide was safe in a large number of patients; adverse effects were

usual dose of isosorbide, which is 2–3 g/kg/day given at intervals of 6–12 h [33, 34].

replacement therapies are required for reducing the adverse effect of ACZ [1].

furosemide for treatment of hydrocephaly [1].

reason, electrolyte levels have to be followed closely [10].

and also are used to reduce intracranial pressure [10, 30].

less, and less frequent biochemical monitoring was required [34].

2.1.3. Combined therapy of furosemide and acetazolamide

2.1.2. Furosemide

80 Hydrocephalus: Water on the Brain

recommended [2, 26–29].

2.2. Osmotic diuretics

2.2.1. Isosorbide

[34–36].

Mannitol is a six-carbon alcohol with a molecular weight of 182. This osmotic agent is not metabolized and is excreted by glomerular filtration, without any important tubular reabsorption or secretion. Also, mannitol induces an increase in serum osmolality and an osmotic gradient between the serum and intracranial compartment. Thus, removal of brain water causes to reduce ICP. Mannitol has been widely used to reduce intracranial and intraocular pressures because of its osmotic diuretic action and presumed antioxidant properties for many years. Mannitol is poorly absorbed from the gastrointestinal tract if administered orally; it would cause osmotic diarrhea, so it must be given parenterally [10, 38–40].

A dose of 0.25–1 g/kg (20% solution) mannitol is administered intravenously and infused over 5 min. Intracranial pressure should fall in 60–90 min [1, 10]. In most cases, after the administration of a bolus of mannitol, intracranial pressure rapidly decreases, but in some patients, it can worsen intracranial hypertension [10].

The effect of mannitol in the treatment of hydrocephaly has been reported in only a few studies. Hayden et al. showed that the administration of mannitol induces rapidly decreased ICP, but this effect lasted only 3–4 h and was followed by a rebound of ICP above baseline [41]. Ma et al. showed that mannitol and corticosteroids represent an effective treatment approach for patients with autoimmune diseases associated with hydrocephaly [42].

Mannitol produces a diuresis more than a natriuresis, and if free water losses are excessive, hypernatremia and hyperkalemia may ensue [10].

#### 2.2.3. Glycerol

Glycerol is an oral osmotic agent, reduces intracranial pressure in adults with brain tumors, and was suggested as a possible agent for managing hydrocephaly [43]. On the contrary, uncontrolled trials did not support its use. Glycerol had no effect in premature infants with hydrocephaly and did not treat hydrocephaly in adults with metastatic brain cancer [44, 45].

#### 2.3. Increasing CSF absorption

#### 2.3.1. Glucocorticoids

Glucocorticoids have been used for decades in a range of neurological disorders associated with raised intracranial pressure [2]. Experimental studies have shown that glucocorticoids reduced CSF production and CSF flow [46, 47]. Glucocorticoids have also been used to reduce the fibrosis in the subarachnoid compartment [2].

In intraventricular hemorrhage (IVH) cases, the blood clot in the ventricular system can interrupt normal CSF flow. After the acute period of the subarachnoid hemorrhage and bacterial or carcinomatous meningitis, cerebrospinal fluid absorption can be reduced. Glucocorticoids can slow this inflammatory response after these conditions. However, steroids do not inhibit fibroblast growth or collagen synthesis. Intrathecal or intravenous steroids have been used to prevent or alleviate arachnoiditis with poor results [1].

and found that intraventricular administration of uPA effectively attenuated ventriculomegaly [52]. Similarly, several empirical studies have shown that intraventricular tPA administration is effective in preventing hydrocephaly after subarachnoid hemorrhage and regressing ventricular dilatation [57]. However, the development of perihematomal edema after tPA administration has increased question mark on this treatment method. Meta-analyses for the comparison of the uPA and tPA regarding the dissolution of the clot after intraventricular hemorrhage were made [58, 59]. Studies have shown that both uPA and tPA cause a decrease

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http://dx.doi.org/10.5772/intechopen.73668

There is a clear relationship between inflammation in the CSF tract and subsequent hydrocephaly development. Anti-inflammatory agents have been experimentally tested to prevent hydrocephaly after meningitis and posthemorrhage. There are numerous studies showing that corticosteroid therapy after acute bacterial meningitis significantly reduces hearing loss and neuroleptic sequelae, but the effects on hydrocephaly development are not fully known. Some studies have shown that the use of steroids does not change the likelihood of developing

Nimodipine is widely used as a calcium channel blocker for the control of hypertension. Experimental studies have shown that nimodipine reduces motor and cognitive function impairment after hydrocephaly [63]. Clinical trials showed that nimodipine is safe, but there is no definitive evidence for the effectiveness in the treatment of hydrocephaly. Magnesium, a

Mechanical factors and reduced white matter blood flow into axonal and oligodendroglial damage can lead to neuropathophysiological damage [65]. Hypoxic changes in proteins of white matter glial and endothelial cells have been found in hydrocephaly by immunohistochemical detection of pimonidazole [66]. Antioxidant therapy is a potential pharmacological treatment for oxidative stress that is associated with brain damage in hydrocephaly. Dietary supplementation of antioxidants like oral coenzyme Q10 (CoQ10), ascorbic acid, glutathione, and lipoic acid in

Neuronal damage in the cortex has been attributed to the disturbed activity of the noradrenergic and dopaminergic neuronal systems and synaptogenesis caused by hydrocephaly [68, 69]. Morphological changes in the hydrocephalic brain with ventricular dilation occur most characteristically in the white matter [70]. Periventricular axons in hydrocephalic brains may sustain the damage in some neurons. Studies on hydrocephaly demonstrated that hippocampal neurons show various secondary abnormalities due to deafferentation [71]. In the immature brain,

humans and animals reduces oxidative stress by decreasing lipid peroxidation [67].

in ventricular volumes, but only uPA improves functional recovery significantly.

hydrocephaly or that this risk can be elevated in children [60–62].

calcium antagonist, also has a weaker protective effect [64].

3.4. Anti-inflammatory therapy

3.5. Vasoactive drugs

3.6. Antioxidative therapy

3.7. Neuron vs axon protection

Some studies have shown that in autoimmune diseases associated with hydrocephaly glucocorticoids have been beneficial and corticosteroids should be considered as first-line treatment choice [42, 48–50].
