Impaired Cerebrospinal Fluid Dynamics Research Articles

Impact of age on the cerebrospinal fluid spaces: high-convexity and medial subarachnoid spaces decrease with age

BackgroundImpaired cerebrospinal fluid (CSF) dynamics may contribute to the pathophysiology of neurodegenerative diseases, and play a crucial role in brain health in older people; nonetheless, such age-related changes have not been well elucidated. Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a neuroimaging phenotype of idiopathic normal-pressure hydrocephalus, originating from impaired CSF dynamics, and closely associated with aging. This study aimed to investigate the pathophysiology of DESH and determine age-related changes in CSF dynamics.MethodsUsing magnetic resonance imaging, we investigated the pathophysiology of DESH by quantitatively evaluating the volumes of DESH-related regions (ventricles [VS], Sylvian fissure [SF], and subarachnoid spaces at high convexity and midline [SHM]) and brain parenchyma in community-dwelling individuals aged ≥ 65 years. DESH-related regions were assessed using a visual rating scale, and volumes measured using voxel-based morphometry. Brain parenchyma volumes were measured using FreeSurfer software.ResultsData from 1,356 individuals were analyzed, and 25 (1.8%) individuals had DESH. Regarding the relationships between the volume of each CSF space and age, VS and SF volumes increased with age, whereas SHM volume did not increase. VS and SF volumes increased as the whole brain volume decreased, whereas SHM volume did not increase even if the whole brain volume decreased; that is, SHM did not expand even if brain atrophy progressed. Moreover, lower Mini-Mental State Examination scores were significantly associated with lower SHM volume and higher VS volume. These associations remained significant even when individuals with DESH were excluded.ConclusionsThis study showed that the volume of high-convexity and medial subarachnoid spaces did not expand and tended to decrease with age; the human brain continuously progresses toward a “DESH-like” morphology with aging in community-dwelling older persons (i.e., DESH might be an “accelerated aging stage” rather than an “age-related disorder”). Our results indicated that brain atrophy may be associated with the development of “DESH-like” morphology. In addition, this morphological change, as well as brain atrophy, is an important condition associated with cognitive decline in older adults. Our findings highlight the importance of investigating the aging process of CSF dynamics in the human brain to preserve brain health in older people.

MRI IN THE ASSESSMENT OF CEREBRAL INJURY AND CEREBROPROTECTIVE EFFECTS OF RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

Objective: The purpose of this single-centre, prospective, comparative study was to evaluate the pattern and severity of the brain structural changes in patients with resistant hypertension (RH) based on MRI assessments and their changes one year after renal denervation (RDN). Design and method: The study comprised 58 patients with RH, aged 52.1 ± 9.1 years, who underwent RDN. Patients underwent office blood pressure measurements, 24-hour blood pressure monitoring, and brain MRI scanning. Using brain MRI, the cerebrospinal fluid (CSF) system measurements, the presence of periventricular leukoaraiosis and focal changes in the brain white matter were evaluated. Results: Initially, patients with RH had a high incidence of the structural brain alterations: 75% with fine focal brain lesions, 75% with impaired CSF dynamics, 23% with sulcal widening, and 90% with periventricular oedema. After RDN, a significant hypotensive effect was noted. According to brain MRI, the number of patients without impaired CSF dynamics did not change significantly: 25% initially, and 20% a year later (χ 2 = 0.63 p = 0.43, and χ2 = 0.72 p = 0.40). The number of patients with grade I impaired CSF dynamics after 6 months significantly increased after 12 months from 50% to 64% (χ2 = 4.00, p = 0.046) due to lowering the number of patients without impaired CSF dynamics and patients with grade II impaired CSF dynamics (χ2 = 1.56, p = 0.21). The number of patients with sulcal widening significantly decreased: from 23% to 8% one year following RDN (χ2 = 40.21 p = 0.000). The incidence of periventricular cerebral oedema did not significantly change one year after the procedure; however, the incidence of fine focal brain lesions significantly decreased (from 75 to 60%, p = 0.02). Conclusions: Thus, it has been revealed that patients with RH are characterised by a high incidence of structural brain alterations based on MRI assessments. A year after bilateral renal denervation, there are significant improvement in intracranial hypertension signs and decrease in the incidence of fine focal brain lesions, without a significant change in the CSF dynamics parameters (Table 1). Figure 1 shows a clinical example of a decrease in the number of fine focal brain lesions after the intervention.

THE MORPHOLOGY OF CHOROID PLEXUSES OF RATS’ BRAIN’S VENTRICLES AT THE FIRST YEAR OF THE DEVELOPMENT

Choroid plexuses of brain ventricles play a special role in the functioning of various brain structures and the formation of cerebrospinal fluid. Through the cerebrospinal fluid, biological, immunological, protective functions are realized. Any deficiency in its production in laboratory animals leads to malnutrition of the brain and spinal cord and impaired adaptive behavior. From this point of view, the study of the features of the structural organization of the choroid plexuses of the ventricles of the brain in laboratory animals in the age aspect seems relevant. The objects of the study were 134 white Wistar rats of different ages - 3, 10, 28 days and 5, 8, 12 months of postnatal development. A histological morphometric study of the choroid plexuses of the ventricles of the brain was carried out. To assess the age-related dynamics of the volume of the cerebral ventricles, sections were selected in which their cross-sectional area was maximum, the values ​​of the indicator were determined on digitized microphotographs with a fourfold increase by tracing the boundaries of the ventricles of subsequent calculations in the Image J morphometric computer program. Determination of volumetric fractions of the choroid plexuses in the ventricles of the brain was carried out stereologically on serial sections using an eyepiece grid with 60 equidistant intersection nodes at a magnification of 400 times. The results of the study indicate that after birth, the choroid plexuses of the ventricles of the brain of Wistar rats develop as an integral tissue system, the most intense changes were noted in the lateral ventricles during the first month of life of the animals. The lateral ventricles are characterized by an accelerated growth in size, outstripping the rate of development of the choroid plexuses. According to the calculations, the increase in the volume of the choroid plexus is largely due to the growth of blood vessels and connective tissue. In the III and IV ventricles, a similar trend is traced, but this process is less pronounced. Since the choroid plexuses are a source of cerebrospinal fluid formation, the revealed quantitative patterns indicate the age-related involution of the ventricles of the brain, which possibly leads to a decrease in the functional activity of their choroid plexuses and impaired cerebrospinal fluid dynamics.

Protective effects of renal denervation based on MRI assessment of the brain in patients with resistant hypertension

Abstract Purpose The purpose of this single-centre, prospective, comparative study was to evaluate the pattern and severity of the brain structural changes in patients with resistant hypertension based on MRI assessments and their changes one year after renal denervation. Material and methods The study comprised 58 patients with resistant hypertension (RH), aged 52.1±9.1 years, who underwent renal denervation (RDN) according to the good clinical practice guidelines. Patients underwent office blood pressure measurements, 24-hour blood pressure monitoring (BPM), and brain MRI scanning. Using brain MRI, the cerebrospinal fluid (CSF) system measurements, in particular the linear measurements of the cerebral lateral ventricles, the linear measurements of the external subarachnoid spaces in 6 regions (in the right and left frontal, parietal, and occipital lobes), sizes of the 3rd and 4th ventricles (length and width), dimensions of intracerebral cisterns (quadrigeminal, prepontine, and chiasmatic), the presence of periventricular leukoaraiosis and focal changes in the brain white matter were evaluated. Results Initially, patients with RH had a high incidence of the structural brain alterations: 75% with fine focal brain lesions, 75% with impaired CSF dynamics, 23% with sulcal widening, and 90% with periventricular oedema. After RDN, a significant hypotensive effect was noted. According to brain MRI, the number of patients without impaired CSF dynamics did not change significantly: 25% initially, and 20% a year later (χ2=0.63 p=0.43, and χ2=0.72 p=0.40). The number of patients with grade I impaired CSF dynamics after 6 months significantly increased after 12 months from 50% to 64% (χ2=4.00, p=0.046) due to lowering the number of patients without impaired CSF dynamics and patients with grade II impaired CSF dynamics (χ2=1.56, p=0.21). The number of patients with sulcal widening significantly decreased: from 23% to 8% one year following RDN (χ2=40.21 p=0.000). The incidence of periventricular cerebral oedema did not significantly change one year after the procedure; however, the incidence of fine focal brain lesions significantly decreased (from 75 to 60%, p=0.02). Conclusion Thus, it has been revealed that patients with RH are characterised by a high incidence of structural brain alterations based on MRI assessments. A year after bilateral renal denervation, there are significant improvement in intracranial hypertension signs and decrease in the incidence of fine focal brain lesions, without a significant change in the CSF dynamics parameters (Table 1). Figure 1 shows a clinical example of a decrease in the number of fine focal brain lesions after the intervention. Funding Acknowledgement Type of funding sources: None.

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.

Normal tension glaucoma in Asia: Epidemiology, pathogenesis, diagnosis, and management.

Normal tension glaucoma (NTG) has similar optic neuropathy as primary open-angle glaucoma (POAG), but intraocular pressure (IOP) is within the normal range. Compared with high-pressure POAG, the development of NTG is possibly a consequence of a complex interaction of several ocular and systemic factors. Recent data have shown higher translaminar pressure gradient due to impaired cerebrospinal fluid dynamics may account for the pathogenic mechanism. Insufficient blood supply and vascular dysregulation may also be the cause of the disease. In clinical evaluation, NTG is a diagnosis by excluding other nonglaucomatous optic neuropathies. NTG is characterized by larger and deeper optic-disc cupping, more central visual field defects and a higher incidence of disc hemorrhage compared with POAG. In clinical practice, controlling IOP as low as possible (with medication, laser trabeculoplasty, or surgery) is the key to manage NTG patients. In addition to IOP reduction, the control of systemic risk factors or improving ocular perfusion may be beneficial therapies. NTG is more prevalent in Asia than in the Western countries. Due to increasing old population and underdiagnoses in the clinical settings, NTG became a great challenge for ophthalmologist in Asia. Therefore, the aim of this article is to focus on the epidemiology, to update pathogenesis, diagnosis, and management for NTG.

Pisa syndrome in Idiopathic Normal Pressure Hydrocephalus

IntroductionIdiopathic Normal Pressure Hydrocephalus (iNPH) is a complex syndrome of ventriculomegaly that can include parkinsonian-like features besides the classical triad of cognitive decline, urinary incontinence, and gait/balance disturbances. Pisa syndrome (PS) is a postural abnormality often associated with parkinsonism and defined as lateral trunk flexion greater than 10° while standing that resolves in the supine position. We reported a case series of classical “fixed” PS and one case of “Metronome” recurrent side-alternating PS in iNPH, displaying opposite electromyographic patterns of paraspinal muscles. MethodsEighty-five iNPH patients were followed longitudinally for at least one year through scheduled clinical and neuropsychological visits. ResultsFive (5.9%) subjects revealed PS. None of them had nigrostriatal dopaminergic involvement detected by [123I]FP-CIT SPECT. Among these patients, four had “fixed” PS, whereas one showed a recurrent side-alternating PS which repeatedly improved after ventriculo-peritoneal shunt and following adjustments of the valve-opening pressure of the shunt system. DiscussionThis is the first case series of PS in iNPH and the first report of “Metronome” PS in iNPH. The prompt response of the abnormal trunk postures through cerebrospinal fluid (CSF) shunt surgery suggests a causative role of an altered CSF dynamics. PS and gait disorders in iNPH could be explained by a direct involvement of cortico-subcortical pathways and subsequent secondary brainstem involvement, with also a possible direct functional damage of the basal ganglia at the postsynaptic level, due to enlargement of the ventricular system and impaired CSF dynamics. The early detection of these cases supports a proper surgical management.

The Importance of the Lymphatic and the Glymphatic System for Glaucoma

Normal tension glaucoma is a variant of primary open angle glaucoma. It is characterized by normal intraocular pressure. Although there are several pathophysiological explanations (e. g. vascular dysregulation, the role of the lamina cribrosa), none of these explanations can fully explain its pathophysiology. The optic nerve is a white matter tract of the brain. It is surrounded by cerebrospinal fluid on its whole length. Neuroradiological examinations hint at a neurodegenerative origin of normal tension glaucoma. Impaired cerebrospinal fluid dynamics and reduced clearance of Aβ amyloid might play a role in this process. The lymphatic and the glymphatic system are thought to be essentially involved.

Perioptic Cerebrospinal Fluid Dynamics in Idiopathic Intracranial Hypertension.

Purpose: To examine the cerebrospinal fluid (CSF) dynamics along the entire optic nerve in patients with idiopathic intracranial hypertension (IIH) and papilledema by computed tomographic (CT) cisternography.Methods: Retrospective analysis of CT cisternographies in 16 patients with a history of IIH and papilledema (14 females and 2 males, mean age: 49 ± 16 years). Contrast loaded CSF (CLCSF) was measured in Hounsfield Units (HU) at three defined regions of interest (ROI) along the optic nerve (orbital optic nerve portion: bulbar and mid-orbital segment, intracranial optic nerve portion) and additionally in the basal cistern. The density measurements in ROI 1, ROI 2, and ROI 3 consist of measurements of the optic nerve complex: optic nerve sheath, CLCSF filled SAS and optic nerve tissue. As controls served a group of patients (mean age: 60 ± 19 years) without elevated intracranial pressure and without papilledema.Results: In IIH patients the mean CLCSF density in the bulbar segment measured 65 ± 53 HU on the right and 63 ± 35 HU on the left side, in the mid-orbital segment 68 ± 37 HU right and 60 ± 21 HU left. In the intracranial optic nerve portion 303 ± 137 HU right and 323 ± 169 HU left and in the basal cistern 623 ± 188 HU. Within the optic nerve the difference of CLCSF density showed a highly statistical difference (p < 0.001) between the intracranial optic nerve portion and the mid-orbital segment. CLCSF density was statistically significantly (p < 0.001) reduced in both intraorbital optic nerve segments in patients with IIH compared to controls.Conclusions: The current study demonstrates reduced CLCSF density within the orbital optic nerve segments in patients with IIH and papilledema compared to 12 controls without elevated intracranial pressure and without papilledema. Impaired CSF dynamics could be involved in the pathophysiology of optic nerve damage in PE in IIH.

Impaired cerebrospinal fluid dynamics along the entire optic nerve in normal-tension glaucoma.

To investigate the cerebrospinal fluid (CSF) dynamics along the entire optic nerve (ON) in patients with normal-tension glaucoma (NTG). Retrospective analysis of computed tomographic (CT) cisternographies in Caucasian patients with NTG. Fifty-six patients (99 of 112 eyes) fulfilled the diagnostic criteria of NTG and underwent CT-cisternography. Twelve subjects without NTG (24 eyes) served as controls. Contrast-loaded cerebrospinal fluid (CLCSF) density measurements in Hounsfield units (HU) were performed at four defined regions along the ON and in the basal cistern. In NTG patients, the mean density CLCSF in the bulbar segment measured 76±49HU right and 88±74HU left, in the mid-orbital segment 117±92HU right and 119±73HU left, in the intracanalicular ON portion 209±88HU right and 216±101HU left, in the intracranial ON portion 290±106HU right and 286±118HU left and in the basal cistern 517±213HU. The distribution of CLCSF along the ON showed a statistically significant reduction in the intraorbital ON segments in NTG patients compared to controls without NTG with the far largest difference within the retrobulbar segment (-150HU right and -117HU left; right: p<0.001, left: p<0.001). This study demonstrates a gradual reduction in CLCSF towards the retrobulbar segment in NTG, while in controls without NTG, no reduction in CLCSF was measured within the orbital segments. Impaired CSF dynamics along the ON may contribute to the pathophysiology of NTG.

Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis.

Normal tension glaucoma (NTG) is an exception in the "glaucoma family" where the major risk factor, increased intraocular pressure, is missing. If not increased intraocular pressure, then what other causes can then lead to glaucomatous optic disc change and visual field loss in NTG? Several possibilities will be discussed. Among them a higher sensitivity to normal pressure, vascular dysregulation, an abnormally high translaminar pressure gradient and a neurodegenerative process due to impaired cerebrospinal fluid dynamics in the optic nerve sheath compartment. There are many excellent review papers published on normal tension glaucoma (NTG). The aim of this paper is therefore not to add another extensive review on NTG but rather to focus on and to discuss some possible mechanisms that are thought to be involved in the pathophysiology of NTG and to discuss the stronger and weaker aspects of each concept. The fact that several concepts exist suggests that NTG is still not very well understood and that no single mechanism on its own might adequately explain NTG.

Alzheimer's Disease-Related Polymorphisms in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a late onset, surgically treated progressive brain disease caused by impaired cerebrospinal fluid dynamics and subsequent ventriculomegaly. Comorbid Alzheimer's disease (AD) seems to be frequent in iNPH. We aim to evaluate the role of AD-related polymorphisms in iNPH. Overall 188 shunt-operated iNPH patients and 688 controls without diagnosed neurodegenerative disease were included into analysis. Twenty-three single-nucleotide polymorphisms (SNPs FRMD4A [rs7081208_A, rs2446581_A, rs17314229_T], CR1, BIN, CD2AP, CLU, MS4A6A, MS4A4E, PICALM, ABCA7, CD33, INPP5D, HLA_DRB5, EPHA1, PTK2B, CELF1, SORL1, FERMT2, SLC24A, DSG2, CASS4, and NME8) adjusted to APOE were analyzed between groups by using binary logistic regression analysis. Neuroradiological characteristics and AD-related changes in the right frontal cortical brain biopsies were available for further analysis. Logistic regression analysis adjusted to age, gender, and other SNPs indicated allelic variation of NME8 between iNPH patients and non-demented controls (p = 0.014). The allelic variation of NME8 was not related to the neuropathological changes in the brain biopsies of iNPH patients. However, periventricular white matter changes (p = 0.017) were more frequent in the iNPH patients with the AA-genotype, an identified risk factor of AD. Our findings increase the evidence that iNPH is characterized by genetic and pathophysiological mechanisms independent from AD. Considering that NME8 plays a role in the ciliary function and displays SNP-related diversity in white matter changes, the mechanisms of NME8 in iNPH and other neurodegenerative processes are worth further study.

Management of Pediatric Pseudotumor Cerebri Syndrome

Pseudotumor cerebri syndrome (PTCS) is a clinical condition characterized by signs and symptoms of elevated intracranial pressure without any radiographic evidence of a mass lesion in the brain, and no abnormalities of the brain parenchyma and cerebrospinal fluid (CSF) composition. Children with PTCS typically present with various combinations of headache, diplopia, and pulsatile tinnitus. Although this syndrome has long been considered a benign condition, it may lead to permanent visual impairment if not promptly and correctly treated. Complete remission of PTCS is associated with a decrease in intracranial pressure, the disappearance of clinical symptoms, and the reversion of papilledema at the funduscopic examination. PTCS has been associated with several comorbidities, but its exact pathophysiology has yet to be fully elucidated. Because the origin of PTCS remains unclear, an etiologically targeted treatment has not yet been identified. Current medical treatments include diuretics (e.g., acetazolamide, furosemide) able to reduce CSF production and pressure, and CSF diversion procedures in the most severe cases. Future elucidation of the pathophysiologic mechanism(s) underlying impaired CSF dynamics in PTCS should help control more finely the CSF formation by choroid plexus with novel drugs having fewer side effects than the commonly used diuretics (e.g., acetazolamide). In this review, we briefly summarize the current therapeutic options in pediatric PTCS.

Ventriculomegaly, delayed myelination, white matter hypoplasia, and “periventricular” leukomalacia: How are they related?

Preterm infants, including some who have sustained intracranial hemorrhage, appear to be at increased risk of lateral ventricular enlargement. Although some occurrences might be due to an impairment of cerebrospinal fluid flow or absorption, many instances of ventriculomegaly without accompanying macrocephaly reflect diffuse white matter damage resulting in diminished (i.e., hypoplastic) white matter or an inadequate density of axons. Perinatally acquired widespread white matter damage is sometimes associated with the focal white matter necrosis. We hypothesize that in some infants both ventriculomegaly and delayed myelination are consequences of disturbances to myelinogenesis that result from an impairment of cells destined to become oligodendroglia or of disturbances to rapidly growing axons. The vulnerability of developing white matter in preterm newborns might, in part, reflect the diminished availability of growth/ survival factors, or a vulnerability to toxins or physillogic perturbations. Awareness that some ventriculomegaly reflects widely distributed white matter damage should prevent overtreatment of what might appear to be hydrocephalus, but is not due to impaired cerebrospinal fluid dynamics. Increased understanding of the phenomena leading to ventriculomegaly related to paucity of white matter should lead to successful efforts to prevent white matter damages in preterm newborns.