Milan Radoš

The influence of body position on cerebrospinal fluid pressure gradient and movement in cats with normal and impaired craniospinal communication

Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension.

Developmental Dynamics of Radial Vulnerability in the Cerebral Compartments in Preterm Infants and Neonates

The developmental vulnerability of different classes of axonal pathways in preterm white matter is not known. We propose that laminar compartments of the developing cerebral wall serve as spatial framework for axonal growth and evaluate potential of anatomical landmarks for understanding reorganization of the cerebral wall after perinatal lesions. The 3-T MRI (in vivo) and histological analysis were performed in a series of cases ranging from 22 postconceptional weeks to 3 years. For the follow-up scans, three groups of children (control, normotypic, and preterms with lesions) were examined at the term equivalent age and after the first year of life. MRI and histological abnormalities were analyzed in the following compartments: (a) periventricular, with periventricular fiber system; (b) intermediate, with periventricular crossroads, sagittal strata, and centrum semiovale; (c) superficial, composed of gyral white matter, subplate, and cortical plate. Vulnerability of thalamocortical pathways within the crossroads and sagittal strata seems to be characteristic for early preterms, while vulnerability of long association pathways in the centrum semiovale seems to be predominant feature of late preterms. The structural indicator of the lesion of the long association pathways is the loss of delineation between centrum semiovale and subplate remnant, which is possible substrate of the diffuse periventricular leukomalacia. The enhanced difference in MR signal intensity of centrum semiovale and subplate remnant, observed in damaged children after first year, we interpret as structural plasticity of intact short cortico-cortical fibers, which grow postnatally through U-zones and enter the cortex through the subplate remnant. Our findings indicate that radial distribution of MRI signal abnormalities in the cerebral compartments may be related to lesion of different classes of axonal pathways and have prognostic value for predicting the likely outcome of prenatal and perinatal lesions.

Effect of osmolarity on CSF volume during ventriculo-aqueductal and ventriculo-cisternal perfusions in cats.

The effect of cerebrospinal fluid (CSF) osmolarity on the CSF volume has been studied on different CSF/brain tissue contact areas. It has been shown, on anesthetized cats under normal CSF pressure, that the perfusion of CSF system (12.96 μl/min) by hyperosmolar CSF (400 mOsml/l) leads to significantly higher outflow volume (μl/min) during ventriculo-cisternal perfusion (29.36 ± 1.17 and 33.50 ± 2.78) than the ventriculo-aqueductal perfusion (19.58 ± 1.57 and 22.10 ± 2.31) in experimental period of 30 or 60 min. Both of these hyperosmolar perfusions resulted in significantly higher outflow volume than the perfusions by isoosmolar artificial CSF (12.86 ± 0.96 and 13.58 ± 1.64). These results suggest that the volume of the CSF depends on both the CSF osmolarity and the size of the contact area between CSF system and surrounding tissue exposed to hyperosmolar CSF. However, all of these facts imply that the control of the CSF volume is not in accordance with the classical hypothesis of cerebrospinal fluid hydrodynamic. According to this hypothesis, the CSF volume should be regulated by active formation of CSF (secretion) inside the brain ventricles and passive CSF absorption outside of the brain. Obtained results correspond to the new hypothesis which claims that the volume of CSF depends on the gradients of hydrostatic and osmotic forces between the blood on one side and extracellular fluid and CSF on the other. The CSF exchange between the entire CSF system and the surrounding tissue should, therefore, be determined by (patho)physiological conditions that predominate within those compartments.

Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development.

The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13–40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries.

Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy

BACKGROUND A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. AIM To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. METHODS MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. RESULTS The HIE patient group showed smaller absolute volumetric data. Statistically significant (p < 0.05) reductions of gyrification index in the right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. CONCLUSIONS Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus.

Experimental Spinal Stenosis in Cats: New Insight in Mechanisms of Hydrocephalus Development

In our new experimental model of cervical stenosis without inflammation we have tested hypothesis that cranio‐spinal communication impairment could lead to hydrocephalus development. Spinal and cranial cerebrospinal fluid (CSF) space separation was obtained with positioning of plastic semiring in epidural space at C2 level in cats. Brain ventricles planimetry, and CSF pressure recording in lateral ventricle (LV) and lumbar subarachnoid space (LSS) were performed in acute and subchronic experiments. In all experiments opening CSF pressures were normal. However, in acute experiments, an infusion of artificial CSF into the LV led to increase of CSF pressure and significant gradient pressure development between LV and LSS due to limited pressure transmission. After 3 or 6 weeks spinal cord atrophy was observed at the site of cervical stenosis, and pressure transmission from LV to LSS was improved as a consequence of spinal tissue atrophy. Planimetry of both the coronal brain slices and the ventricles’ surface showed that control ventricular surface was 0.6 ± 0.1% (n = 5), and 1.6 ± 0.2% (n = 4) in animals with subchronic cervical stenosis (P < 0.002). These results support the mentioned hypothesis claiming that CSF volume cranio‐spinal displacement impairment could start pathophysiological processes leading to development of hydrocephalus.

Spinal contribution to CSF pressure lowering effect of mannitol in cats.

OBJECTIVES After application of hyperosmolar mannitol the cerebrospinal (CSF) pressure is usually lowered within 30 min but this effect cannot be explained either by changes in intracranial blood volume and flow or by changes in brain volume. We assume that this effect of mannitol my be consequence of CSF volume decrease primarily in the spinal CSF due to high compliance of the spinal dura. METHODS To explore such a possibility we planned to separate spinal and cerebral CSF. In chloralose anaesthetized cats dorsal laminectomy of C2 vertebrae was performed and a plastic semi ring was positioned extradurally separating cranial and spinal CSF. CSF pressures were recorded via cannulas positioned in lateral ventricle and lumbar subarachnoid space at L3 vertebrae, respectively. RESULTS After intravenous bolus of 20% mannitol (0.5 or 1.0 g/kg/ 3 min) in control animals without cervical stenosis, the fall of both ventricular and lumbar CSF pressures was equal over time. At 15 min after mannitol application in cats with cervical stenosis an slight increase of ventricular and a fall of lumbar CSF pressures were observed, while at 30 min a gradient of these pressures of 5.5 and 7 cm H2O at lower and higher dose of mannitol, respectively, were registered. However, after removal of cervical stenosis these gradients disappeared. CONCLUSION The observed changes of CSF pressures in spinal and intracranial space indicate that spinal subarachnoid space contributes a great deal to overall fall of CSF pressure and volume in the early period after mannitol application probably due to high compliance of the spinal dura.

Cerebrospinal fluid secretion by the choroid plexus

to the editor: In their review, “Cerebrospinal fluid secretion by the choroid plexus,” Damkier, Brown, and Praetorius ([3][1]) aimed to present recent advances in understanding the regulation of cerebrospinal fluid (CSF) secretion and limitations of current understanding of CSF formation and

Psychotic reaction as a manifestation of multiple sclerosis relapse treated with plasma exchange

We present a patient with a clinically isolated syndrome suggestive of multiple sclerosis, who developed a full-blown picture of paranoid psychosis with suicidal attempt. Four new lesions were observed on brain MRI, one in the left and one in the right temporal lobe, one subcortically in the cingulate gyrus and one centrally in the tegmentum of the midbrain. The patient was treated with plasma exchange and recovered completely. Psychosis is not so rare symptom of multiple sclerosis as previously reported, and poses a major treatment challenge. A combination of lesions at strategic locations was a presumed mechanism of psychosis in this patient.

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.