The Effect of Body Position on Intraocular and Intracranial Pressure in Rabbits.

BACKGROUND: The correlation between cerebrospinal fluid (CSF) and intraocular pressure (IOP) is still unclear. We compared CSF and IOP measured by the same invasive technique using a new experimental model in rabbits during changes of body position. METHODS: Pressure changes were recorded in the lateral ventricle (LV), the cortical subarachnoid space (CSS), and the anterior ocular chamber of anesthetized rabbits (n = 12). Animals and measuring instruments were both fixed on a board at an adequate hydrostatic level. RESULTS: In a horizontal position, control IOP (15.1 ± 1.6 cmH2O) and CSF pressure in the LV (12.4 ± 0.6 cmH2O) and CSS (12.2 ± 0.9 cmH2O) were similar during the 60-min period. When changing the body position from horizontal to vertical (upright), CSF pressures decreased drastically (LV = -5.5 ± 2.6 cmH2O and CSS = -7.7 ± 2.3 cmH2O), while the IOP decreased moderately (IOP = 13.3 ± 0.5 cmH2O). CONCLUSION: Change in body position from horizontal to vertical causes drastic changes in CSF pressure and moderate changes in IOP. Thus, IOP is not reflected by the CSF pressure. In an upright position, the values of CSF pressure were equal to the hydrostatic distance between measuring points and the foramen magnum, which suggests that CSF pressure inside the cranium depends on its anatomical and biophysical features, and not on CSF secretion and absorption.

Long lasting near-obstruction stenosis of mesencephalic aqueduct without development of hydrocephalus--case report.

The aim of this study is to present the five-year longitudinal magnetic resonance imaging (MRI) follow up of a patient with incidental finding of near-obstruction stenosis of the aqueduct of Sylvius due to a large pineal cyst. The patient was scanned 3 times on a 3T MR device using a set of standard structural sequences supplemented with high-resolution constructive interference of steady state (CISS) T2 sequence for precise delineation of the aqueduct of Sylvius and cardiac-gated phase-contrast sequences for the analysis of cerebrospinal fluid (CSF) movement. On all MR scans, the size of the pineal cyst and severity of near-obstruction aqueductal stenosis did not show any morphological changes. There was no significant ventricular enlargement although structural CISS sequence showed a near-obstruction stenosis and cardiac-gated phase-contrast sequences did not detect CSF movement through the aqueduct of Sylvius. Our findings are contradictory to the classic hypothesis of CSF physiology based on secretion, circulation, and absorption of CSF, which states that the impairment of CSF circulation through the aqueduct of Sylvius inevitably leads to a hypertensive hydrocephalus development involving the third and the lateral ventricle. Our research group previously proposed a new hypothesis of CSF physiology, which offers more suitable explanation for such clinical cases.

Changes of cerebrospinal fluid pressure gradient in different body positions under experimental impairment of cerebrospinal fluid pathway: new insight into hydrocephalus development.

It is generally accepted that hydrocephalus is a consequence of the disbalance between cerebrospinal fluid (CSF) secretion and absorption which should in turn lead to CSF pressure gradient development and ventricular enlargement. To test CSF pressure gradient role in hydrocephalus development, we experimentally caused CSF system impairment at two sites in cats. In the first group of animals, we caused Sylvian aqueduct obstruction and recorded CSF pressure changes pre and post obstruction at three measuring sites (lateral ventricle -LV, cortical-CSS and lumbar subarachnoid space -LSS) during 15 min periods and in different body positions over 360 degrees. In the second group of experiments, we caused cervical stenosis by epidural plastic semiring implantation and monitored CSF pressure changes pre and post stenosis implantation at two measuring sites (lateral ventricle and lumbar subarachnoid space) during 15 min periods in different body positions over 360 degrees. Both groups of experimental animals had similar CSF pressures before stenosis or obstruction at all measuring points in the horizontal position. During head-up verticalization, CSF pressures inside the cranium gradually became more subatmospheric with no significant difference between LV and CSS, as they are measured at the same hydrostatic level, while CSF pressure inside LSS became more positive, causing the development of a large hydrostatic gradient between the cranial and the spinal space. With cervical stenosis, CSF pressure inside the cranium is positive during head-up verticalization, while in cats with aqueductal obstruction CSF pressure inside the CSS remains negative, as it was during control period. Concomitantly, CSF pressure inside LV becomes less negative, thus creating a small hydrostatic gradient between LV and CSS. Since CSF pressure and gradient changes occur only by shifting body position from the horizontal plane, our results indicate that cervical stenosis in a head-up vertical position reduces blood perfusion of the whole brain, while aqueductal obstruction impairs only the perfusion of the local periventricular brain tissue. It seems that, for evolutionary important bipedal activity, free craniospinal communication and good spinal space compliance represent crucial biophysical parameters for adequate cerebral blood perfusion and prevention of pathophysiological changes leading to the development of hydrocephalus.

The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity.

We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application.

Predictive value of spinal CSF volume in the preoperative assessment of patients with idiopathic normal-pressure hydrocephalus.

Introduction: The pathophysiology, diagnosis, and management of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Although some prognostic tests recommended in iNPH guidelines should have high sensitivity and high predictive value, there is often no positive clinical response to surgical treatment. Materials and methods: In our study, 19 patients with clinical and neuroradiological signs of iNPH were selected for preoperative evaluation and possible further surgical treatment according to the guidelines. MR volumetry of the intracranial and spinal space was performed. Patients were exposed to prolonged external lumbar drainage in excess of 10 ml per hour during 3 days. Clinical response to lumbar drainage was assessed by a walk test and a mini-mental test. Results: Twelve of 19 patients showed a positive clinical response and underwent a shunting procedure. Volumetric values of intracranial space content in responders and non-responders showed no statistically significant difference. Total CSF volume (sum of cranial and spinal CSF volumes) was higher than previously published. No correlation was found between spinal canal length, CSF pressure, and CSF spinal volume. The results show that there is a significantly higher CSF volume in the spinal space in the responder group (n = 12) (120.5 ± 14.9 ml) compared with the non-responder group (103.1 ± 27.4 ml; n = 7). Discussion: This study demonstrates for the first time that CSF volume in the spinal space may have predictive value in the preoperative assessment of iNPH patients. The results suggest that patients with increased spinal CSF volume have decreased compliance. Additional prospective randomized clinical trials are needed to confirm our results.

Stable Gastric Pentadecapeptide BPC 157-Possible Novel Therapy of Glaucoma and Other Ocular Conditions.

Recently, stable gastric pentadecapeptide BPC 157 therapy by activation of collateral pathways counteracted various occlusion/occlusion-like syndromes, vascular, and multiorgan failure, and blood pressure disturbances in rats with permanent major vessel occlusion and similar procedures disabling endothelium function. Thereby, we revealed BPC 157 cytoprotective therapy with strong vascular rescuing capabilities in glaucoma therapy. With these capabilities, BPC 157 therapy can recover glaucomatous rats, normalize intraocular pressure, maintain retinal integrity, recover pupil function, recover retinal ischemia, and corneal injuries (i.e., maintained transparency after complete corneal abrasion, corneal ulceration, and counteracted dry eye after lacrimal gland removal or corneal insensitivity). The most important point is that in glaucomatous rats (three of four episcleral veins cauterized) with high intraocular pressure, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, nor- mal retinal and choroidal blood vessel presentation, and normal optic nerve presentation. The one episcleral vein rapidly upgraded to accomplish all functions in glaucomatous rats may correspond with occlusion/occlusion-like syndromes of the activated rescuing collateral pathway (azygos vein direct blood flow delivery). Normalized intraocular pressure in glaucomatous rats corresponded to the counteracted intra-cranial (superior sagittal sinus), portal, and caval hypertension, and aortal hypotension in occlusion/occlusion-like syndromes, were all attenuated/eliminated by BPC 157 therapy. Furthermore, given in other eye disturbances (i.e., retinal ischemia), BPC 157 instantly breaks a noxious chain of events, both at an early stage and an already advanced stage. Thus, we further advocate BPC 157 as a therapeutic agent in ocular disease.

Stable Gastric Pentadecapeptide BPC 157 May Recover Brain-Gut Axis and Gut-Brain Axis Function.

Conceptually, a wide beneficial effect, both peripherally and centrally, might have been essential for the harmony of brain-gut and gut-brain axes' function. Seen from the original viewpoint of the gut peptides' significance and brain relation, the favorable stable gastric pentadecapeptide BPC 157 evidence in the brain-gut and gut-brain axes' function might have been presented as a particular interconnected network. These were the behavioral findings (interaction with main systems, anxiolytic, anticonvulsive, antidepressant effect, counteracted catalepsy, and positive and negative schizophrenia symptoms models). Muscle healing and function recovery appeared as the therapeutic effects of BPC 157 on the various muscle disabilities of a multitude of causes, both peripheral and central. Heart failure was counteracted (including arrhythmias and thrombosis), and smooth muscle function recovered. These existed as a multimodal muscle axis impact on muscle function and healing as a function of the brain-gut axis and gut-brain axis as whole. Finally, encephalopathies, acting simultaneously in both the periphery and central nervous system, BPC 157 counteracted stomach and liver lesions and various encephalopathies in NSAIDs and insulin rats. BPC 157 therapy by rapidly activated collateral pathways counteracted the vascular and multiorgan failure concomitant to major vessel occlusion and, similar to noxious procedures, reversed initiated multicausal noxious circuit of the occlusion/occlusion-like syndrome. Severe intracranial (superior sagittal sinus) hypertension, portal and caval hypertensions, and aortal hypotension were attenuated/eliminated. Counteracted were the severe lesions in the brain, lungs, liver, kidney, and gastrointestinal tract. In particular, progressing thrombosis, both peripherally and centrally, and heart arrhythmias and infarction that would consistently occur were fully counteracted and/or almost annihilated. To conclude, we suggest further BPC 157 therapy applications.

Dependence of cerebrospinal fluid pressure and volume on the changes in serum osmolarity in cats.

OBJECTIVES: To study the effect of blood osmolarity on cerebrospinal fluid (CSF) volume and CSF pressure in cats. METHODS: Three types of methods were used on anesthetized cats. The first, ventriculo-cisternal perfusion (12.96 µL/min) before and after i.v. application of 20% mannitol; the second, measuring the outflow of CSF by cisternal free drainage; and the third, measuring CSF pressure in the ventricles of an intact CSF system, with the second and third method being performed before and after the i.p. application of a hypo-osmolar substance (distilled water). RESULTS: In the first group, the application of 20% mannitol led to a significantly reduced (p < 0.005) outflow volume (from 12.60 ± 0.29 to 0.94 ± 0.09 µL/min). In the second group, the outflow CSF volume significantly increased (p < 0.001) after the application of distilled water (from 18.8 ± 0.3 to 28.2 ± 0.7 µL/min). In the third group, after the application of distilled water, the CSF pressure also significantly increased (p < 0.05; from 8.3 ± 0.8 to 16.1 ± 0.14 cm H(2)O). CONCLUSION: We conclude that changes in serum osmolarity change the CSF volume because of the osmotic gradient between the blood and all of the CSF compartments, and also that the change in CSF pressure is closely associated with changes in CSF volume.

The effect of body position on intraocular and CSF pressures in the lateral ventricle, and in cortical and lumbar subarachnoid spaces in cats.

BACKGROUND: Correlation between cerebrospinal fluid (CSF) and intraocular pressure (IOP) is still unclear. We compared CSF pressure from different parts of the CSF system and IOP measured by the same invasive technique in a new experimental model in cats during changes of body position. METHODS: Pressure changes were recorded on anesthetized cats (n = 7) in the lateral ventricle (LV), in the cortical (CSS) and lumbar (LSS) subarachnoid spaces, and in the anterior ocular chamber. Animals and measuring instruments were both fixed on a board at an adequate hydrostatic level. RESULTS: In a horizontal position, IOP (18.5 ± 0.6 cm H(2)O) and CSF pressures (LV = 17.4 ± 0.9; CSS = 17.2 ± 0.7; LSS = 17.8 ± 1.2 cm H(2)O) were similar. In a vertical position, pressure in the LSS increased (33.5 ± 2.3 cm H(2)O), pressures inside the cranial cavity dropped (LV = -4.1 ± 0.9 cm H(2)O; CSS = -4.8 ± 0.5 cm H(2)O), while IOP slightly decreased (14.3 ± 0.1 cm H(2)O). CONCLUSION: Change in body position from horizontal to upright causes drastic changes in CSF pressure and relatively small changes in IOP, which indicates that the IOP does not reflect CSF pressure. In an upright position, CSF pressures were equal at the same hydrostatic level in LV and CSS, which suggests that CSF pressure inside the cranium depends on its anatomical and biophysical features, and not on CSF secretion and absorption.

Cerebrospinal fluid micro-volume changes inside the spinal space affect intracranial pressure in different body positions of animals and phantom.

Interpersonal differences can be observed in the human cerebrospinal fluid pressure (CSFP) in the cranium in an upright body position, varying from positive to subatmospheric values. So far, these changes have been explained by the Monroe-Kellie doctrine according to which CSFP should increase or decrease if a change in at least one of the three intracranial volumes (brain, blood, and CSF) occurs. According to our hypothesis, changes in intracranial CSFP can occur without a change in the volume of intracranial fluids. To test this hypothesis, we alternately added and removed 100 or 200 µl of fluid from the spinal CSF space of four anesthetized cats and from a phantom which, by its dimensions and biophysical characteristics, imitates the cat cerebrospinal system, subsequently comparing CSFP changes in the cranium and spinal space in both horizontal and vertical positions. The phantom was made from a rigid "cranial" part with unchangeable volume, while the "spinal" part was made of elastic material whose modulus of elasticity was in the same order of magnitude as those of spinal dura. When a fluid volume (CSF or artificial CSF) was removed from the spinal space, both lumbar and cranial CSFP pressures decreased by 2.0-2.5 cm H2O for every extracted 100 µL. On the other hand, adding fluid volume to spinal space causes an increase in both lumbar and cranial CSFP pressures of 2.6-3.0 cm H2O for every added 100 µL. Results observed in cats and phantoms did not differ significantly. The presented results on cats and a phantom suggest that changes in the spinal CSF volume significantly affect the intracranial CSFP, but regardless of whether we added or removed the CSF volume, the hydrostatic pressure difference between the measuring sites (lateral ventricle and lumbar subarachnoid space) was always constant. These results suggest that intracranial CSFP can be increased or decreased without significant changes in the volume of intracranial fluids and that intracranial CSFP changes in accordance with the law of fluid mechanics.

Fourier Transform Infrared Spectroscopy Reveals Molecular Changes in Blood Vessels of Rats Treated with Pentadecapeptide BPC 157.

Recently, it was found that when confronted with major vessel occlusion and vascular failure, stable gastric pentadecapeptide BPC 157 therapy might rapidly functionally improve minor vessels to take over the function of disabled major vessels, reorganize blood flow, and compensate failed vessel function. We focused on the BPC 157 therapy effect obtained by giving 10 ng/kg ip to rats 5 min before sacrifice on the rat thoracic aorta, which we assessed with Fourier transform infrared spectroscopy (FTIR) 90 min thereafter. We applied a principal component analysis (PCA). The PCA model showed, with a clear distinction being mostly due to the PC1 score, differences between the spectra of BPC 157- and saline-treated rats. The comparison of the averaged spectra of these two groups with their differential spectrum and PC loadings allowed us to identify the parts of the FTIR spectra that contributed the most to the spectral separation of the two observed groups. The PC1 loadings and the differential spectrum showed that the main bands affecting the separation were the amid I band around 1650 cm-1, the amid II band around 1540 cm-1, and the vibrational band around 1744 cm-1. Fitting the spectral range between 1450 and 1800 cm-1 showed changes in protein conformation and confirmed the appearance of the vibrational band at 1744 cm-1. Controls had a substantially more intense vibrational band at 1744 cm-1. These spectral results showed the cells from saline-treated (control) rats to be in the early stage of cell death, while the samples from BPC 157-rats were protected. Thus, BPC 157 therapy changed the lipid contents and protein secondary structure conformation, with a rapid effect on vessels, within a short time upon application.

Physical characteristics in the new model of the cerebrospinal fluid system.

It is unknown which factors determine the changes in cerebrospinal fluid (CSF) pressure inside the craniospinal system during the changes of the body position. To test this, we have developed a new model of the CSF system, which by its biophysical characteristics and dimensions imitates the CSF system in cats. The results obtained on a model were compared to those in animals observed during changes of body position. A new model was constructed from two parts with different physical characteristics. The "cranial" part is developed from a plastic tube with unchangeable volume, while the "spinal" part is made of a rubber baloon, with modulus of elasticity similar to that of animal spinal dura. In upright position, in the "cranial" part of the model the negative pressure appears without any measurable changes in the fluid volume, while in "spinal" part the fluid pressure is positive. All of the observed changes are in accordance to the law of the fluid mechanics. Alterations of the CSF pressure in cats during the changes of the body position are not significantly different compared to those observed on our new model. This suggests that the CSF pressure changes are related to the fluid mechanics, and do not depend on CSF secretion and circulation. It seems that in all body positions the cranial volume of blood and CSF remains constant, which enables a good blood brain perfusion.

Potential error in ventriculocisternal perfusion method for determination of cerebrospinal fluid formation rate in cats.

The cerebrospinal fluid (CSF) formation rate (Vf) has been extensively studied by the ventriculocisternal perfusion, a method still regarded as the most precise one. This method as well as the equation for the calculation of the CSF formation rate (Vf) was established by Heisey et al on indicator dilution in perfusate. They assumed that the dilution of the indicator substance in perfusion is a consequence of newly formed CSF i.e. a higher CSF formation rate would result in a higher degree of dilution of the indicator substance. Therefore, such method is indirect and any mistake in the interpretation of the degree of indicator dilution would lead to questionable and often contradictory results regarding CSF formation rates. According to Heisey's equation, Vf shoud not depend on the rate of ventriculocisternal perfusion. However it has been shown that Vf is perfusion dependt value, and also that during perfusion the indicator substance is partially absorbed into surrounding tissue. It is possible that obtained Vf dependence on perfusion rate was caused by observed absorption of indicator substances. For that reason, in anaesthetised cats ventriculocisternal perfusion was performed at higher (252.0 microL/min) and at lower perfusion rate (65.5 microL/min) and Vf was calculated at both experimental and corrected (just for absorbed amount) values of indicator substance. Since (inspite of the correction) the difference of 12.4 microL/min between lower (15.0 microL/min) and higher perfusion rate (27.4 microL/min) was obtained, it is obvious that ventriculocisternal perfusion method cannot be considered reliable for measuring CSF formation rate.

Methods for measuring acoustic power of an ultrasonic neurosurgical device.

Measurement of the acoustic power in high-energy ultrasonic devices is complex due to occurrence of the strong cavitation in front of the sonotrode tip. In our research we used three methods for characterization of our new ultrasonic probe for neuroendoscopic procedures. The first method is based on the electromechanical characterization of the device measuring the displacement of the sonotrode tip and input electrical impedance around excitation frequency with different amounts of the applied electrical power The second method is based on measuring the spatial pressure magnitude distribution of an ultrasound surgical device produced in an anechoic tank. The acoustic reciprocity principle is used to determinate the derived acoustic power of equivalent ultrasound sources at frequency components present in the spectrum of radiated ultrasonic waves. The third method is based on measuring the total absorbed acoustic power in the restricted volume of water using the calorimetric method. In the electromechanical characterization, calculated electroacoustic efficiency factor from equivalent electrical circuits is between 40-60%, the same as one obtained measuring the derived acoustic power in an anechoic tank when there is no cavitation. When cavitation activity is present in the front of the sonotrode tip the bubble cloud has a significant influence on the derived acoustic power and decreases electroacoustic efficiency. The measured output acoustic power using calorimetric method is greater then derived acoustic power, due to a large amount of heat energy released in the cavitation process.

Hydroxyapatite ceramics in multilevel cervical interbody fusion - is there a role?

The aim of this study is to evaluate the efficacy of hydroxyapatite grafts in multilevel cervical interbody fusion during the one year follow-up. A total of 86 patients with degenerative cervical disc disease underwent all together 224 cervical interbody fusion procedures in which either Smith-Robinson or Cloward type hydroxyapatite grafts were used. The surgeries included radiculopathy in 38 cases, myelopathy in 20 cases and myeloradicuopathy in 28 patients. In 65 out of 86 patients, fusion was followed by an anterior instrumentation (plating). Postoperatively, patients were followed for a mean of 15.64 (range 11-23.3) months. All patients underwent radiography to evaluate fusion and the axis curvature. Excellent clinical results (86%), described as a complete or partial relief of symptoms with full return to preop activity, were obtained in patients with radiculopathy. There were 5 grafts mobilizations and one graft fracture. Two grafts extruded in non-instrumented patients and required repeated surgery. There were other three reoperations due to the hardware problems. One year fusion rate was obtained at 86% for two-level surgery, 80.1% for three-level surgery and 74% for four-level surgery. The mean (SD) hospital stay was 3.8 (0.7) days. A hydroxyapatite cheramic can be a very effective synthetic material for multilevel cervical interbody fusion. It is characterized by a high fusion rate and a small percentage of graft-related complications, especially when fusion procedure is followed by plating.

New Insight into the Mechanism of Mannitol Effects on Cerebrospinal Fluid Pressure Decrease and Craniospinal Fluid Redistribution.

Intracranial hypertension, which often follows a severe brain injury, is usually treated with intravenous (i.v.) application of hyperosmolar solutions. The mechanism of intracranial cerebrospinal fluid (CSF) pressure decrease after such a treatment is still unclear. The aim of this article was to try to explain the mechanism of CSF pressure reduction after i.v. hyperosmolar mannitol bolus in regard to the changes in CSF volume. Two types of experiments were done on anesthetized cats before and after hyperosmolar mannitol application: ventriculo-cisternal perfusion at different perfusion rates, simultaneously measuring the perfusate outflow volume, and CSF pressure recording in the lateral ventricle before and during artificial CSF infusion. Mannitol application in the first group of cats significantly reduced collected prefusate volume during ventriculo-cisternal perfusion, and in the second group it prevented CSF pressure increase caused by artificial CSF infusion. Our results strongly suggest that the mechanism of hyperosmolar mannitol action after its i.v. application is based on osmotic fluid retrieval from interstitial and cerebrospinal compartments into the microvessels. This shift, without significant volume change inside the cranium, causes a predominant decrease of CSF volume in the spinal part of the system, which in turn leads to lowering of the CSF pressure. Spinal CSF volume decrease is enabled by the extensibility of the spinal dura, this way providing the possibility for CSF volume redistribution inside the CSF system, together with CSF pressure decrease. This mechanism of mannitol action is in accordance with the new hypothesis of CSF physiology.

Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes.

BACKGROUND: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting. OBJECTIVE: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients. METHODS: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer's disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups. RESULTS: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = -0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion. CONCLUSION: Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.

Intravenous dexamethasone in acute management of vestibular neuritis: a randomized, placebo-controlled, single-blind trial.

INTRODUCTION: The aim of the present study was to evaluate the role of intravenous dexamethasone in relieving the symptoms and signs of vestibular neuritis in the emergency department setting. PATIENTS AND METHODS: This was a randomized, placebo-controlled, superiority, single-blind study. Patients were randomized either to intravenous dexamethasone (group A) or to placebo (group B), with all patients receiving symptomatic therapy. The primary outcome was defined as necessity to hospitalize patients who present with vestibular neuritis in the emergency department. The secondary outcomes were (a) improvement in nystagmus, (b) improvement in postural instability, (c) lessening of nausea, (d) lessening of vomiting, and (e) recovery of subjective symptoms. RESULTS: Altogether, 100 patients were randomized, 51 into group A and 49 into group B. There was no difference in the hospitalization rate between groups (P=0.284). In both groups, there was a statistically significant difference in the values of all measured variables 2 h after therapy intervention compared with the baseline values. In group A, significantly fewer patients had third-degree nystagmus 2 h after therapy intervention whereas the difference in group B did not reach statistical significance. After therapy, more patients had first-degree nystagmus in group A as well as in group B than before the intervention. There was a significantly greater absolute difference in European Evaluation of Vertigo scale results in group A compared with group B. CONCLUSION: The value of dexamethasone cannot be established, given the small sample and limitations of the present study. Some observations consistent with clinical improvement cannot exclude a true treatment effect, and further study is still warranted.