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Idiopathic intracranial hypertension: The veno glymphatic connections
Abstract
The recent discoveries of the glymphatic and lymphatic systems of the brain have helped advance our understanding of CSF physiology and may allow new insights in the understanding of idiopathic intracranial hypertension (IIH). The clinical and radiologic presentations of IIH appear to be related to congestion of the glymphatic system associated with an overflow of the lymphatic CSF outflow pathway. By revisiting the role of "vascular arachnoid granulations" in the brain, we hypothesize that an initial impairment of the transport of interstitial fluid from the glymphatic system to the venous blood of the dural sinuses may trigger the hydrodynamic cascade of IIH. Furthermore, we speculate that, similar to other water-exchange systems in the brain, a specific subtype of aquaporin is involved in this transport. This theory may eventually help to provide an underlying explanation for IIH and its associated conditions, since in most of them, the expression of several aquaporins is altered.
... Conventional theory suggests that CSF absorption through arachnoid granulations is due to a pressure differential [1]. Arachnoid granulations are pia mater's extension into dural venous sinuses distributed throughout the sinus and are most prominent in sagittal and transverse sinuses [2]. They appear similar to grapes growing into the vessel lumen. ...
... Reabsorption also occurs through the lymphatic sheaths of small vessels of the cranial pia mater as well as the perineural sheaths of the cranial and spinal nerves. It is hypothesized that impaired glymphatic drainage due to inflammation from obesity may result in congestion of the lymphatic pathway, increasing the CSF of the interstitial space and causing excess CSF to flow into the veins that travel out of the brain [2]. As the skull can only accommodate a fixed volume, the buildup of CSF results in elevated intracranial pressure. ...
... Pulsatile tinnitus is also often seen in the setting of idiopathic intracranial hypertension (IIH). IIH can be summarized in a pathological triad consisting of restriction of the venous CSF outflow pathway and congestion of the glymphatic system [2,9]. Dandy proposed the original diagnostic criteria for the diagnosis of IIH. ...
Dural venous sinus stenting is an emerging and exciting area in otolaryngology in collaboration with neurosurgeons and neuroradiologists. The first cases were reported 20 years ago. It is now considered part of the routine treatment of increased intracranial pressure due to transverse sinus stenosis. ENT doctors are the first to see these patients in their clinics, as sinus headaches, pulsating tinnitus, and dizziness are the most common symptoms. Previously, with limited success, high-dose diuretics and intracranial shunts had been the only options for treating these patients. Other methods, such as covering the sigmoid sinuses with graft material, appear to cause a sudden increase in intracranial pressure that can lead to blindness and even death. This overview summarizes the clinical and imaging characteristics of patients who will benefit from endovascular sinus stenting for elevated intracranial pressure.
... 6 Recently, a developing hypothesis is that IIH may be a result of dysfunctional cerebral glymphatic clearance with impaired clearance of cerebral interstitial fluid (ISF), resulting in accumulation of intracranial pressure. 7,8 However, to date, only a few studies have been completed demonstrating impaired glymphatic function in IIH. [9][10][11][12] Furthermore, there have been no studies investigating how TSS is related to glymphatic outflow in IIH. ...
... Alternatively, intrinsic TSS may reduce venoglymphatic outflow with consequential secondary glymphatic dysfunction, impaired efflux, and ISF accumulation. [6][7][8]12 To noninvasively study the glymphatic system, an MRI-based technique called diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has recently been used to image and quantify glymphatic function in patients. 13,14 Although there is no clear consensus on the best neuroimaging method for investigating the glymphatic system in humans, a particular advantage of DTI-ALPS is that it enables the quantification of glymphatic clearance without the need for intravascular contrast agents and can also be completed retrospectively on previously completed MRIs. ...
... 4,21 A few studies and groups have suggested that IIH is a "glymphedema" of the brain, possibly because of glymphatic system dysfunction. [7][8][9][10][11][12] In fact, we have previously shown that compared with healthy controls, patients with IIH possess impaired glymphatic flow that is directly proportional to clinical severity of papilledema, 12 which also aligns with the observation that IIH patients with visual symptoms demonstrate lower glymphatic clearance ( Figure 3D). We build on our work by demonstrating, for the first time, a direct connection between the degree of abnormal glymphatic outflow in IIH and the extent of venous sinus stenosis, connecting 2 seemingly unrelated variables involved in IIH pathomechanism. ...
Background and objectives:
Idiopathic intracranial hypertension (IIH) is a neurologic disorder characterized by symptoms of elevated intracranial pressure in the absence of a clear cause. There is a developing theory that IIH may, in part, be related to abnormal cerebral glymphatic clearance. In addition, transverse sinus stenosis (TSS) is a common finding in IIH of unclear pathophysiologic significance. Similarly, whether or not TSS is associated with glymphatic outflow in IIH is unknown. The aim of this investigation was to explore the possible association between glymphatic outflow and extent of TSS in patients with IIH.
Methods:
The study cohort consisted of patients with IIH and healthy controls who were retrospectively identified from our tertiary care institution located in upstate New York from 2016 to 2023. Patients with IIH were included if they had brain MRIs completed with sufficient sequences for analysis. Brain MRIs were computationally analyzed using diffusion tensor imaging analysis along the perivascular space technique to quantify the glymphatic function in patients with IIH. Glymphatic clearance, the primary outcome, was then correlated with the degree of TSS on MR venography using 2 different scoring systems, the 'Farb score' and 'Carvalho score.'
Results:
Overall, 81 patients with IIH (70 [86%] female, mean age 29.8 years [SD: 8.2 years], mean BMI 41 [SD: 8.4]) and 10 normal controls were identified with sufficient imaging. Based on the Carvalho TSS score, IIH patients without TSS had significantly lower glymphatic clearance than healthy controls (mean ALPS index: 1.196 [SD: 0.05] vs 1.238 [SD: 0.04], respectively; p = 0.018). Furthermore, IIH patients with TSS had significantly lower glymphatic outflow than healthy controls (1.129 [SD: 0.07] vs 1.238 [SD: 0.04], respectively; p < 0.0001) and IIH patients without TSS (1.129 [SD: 0.07] vs 1.196 [SD: 0.05], respectively; p < 0.0001). In addition, there was a significant association between increasing extent of TSS and declining glymphatic clearance (p < 0.0001, R = 0.62). Finally, IIH patients with severe TSS had significantly lower glymphatic flow than IIH patients with mild stenosis (1.121 [SD: 0.07] vs 1.178 [SD: 0.05], respectively; p < 0.0001). These findings were similarly recapitulated using the Farb TSS scoring system.
Discussion:
These preliminary findings suggest that the extent of TSS is associated with the degree of glymphatic clearance in IIH, providing novel insights into IIH pathophysiology. Further research is required to clarify the possible causal relationship between TSS and impaired glymphatic clearance in IIH.
... A small number of groups have recently theorized that IIH might primarily be a consequence of abnormally functioning cerebral glymphatics with impaired clearance of CSF and cerebral interstitial fluid. [2][3][4] Broadly, the cerebral glymphatic system is a "brainwide pathway for fluid transport, which includes the para-arterial influx of subarachnoid CSF into the brain interstitium, followed by clearance of interstitial fluid along large-caliber draining veins." 5 Nonetheless, experimental evidence supporting the dysfunctional glymphatic model for IIH remains sparse, largely due to a paucity of methods to measure glymphatic flow within the human brain. ...
... 2,3 Likewise, some have postulated a link between aquaporin-4 (AQP4) alterations and impaired glymphatic outflow resulting in IIH. 2,15 However, this hypothesis is largely theoretical with limited experimental evidence to substantiate that glymphatic dysfunction is actually present in IIH. One of the reasons for this is a paucity of methods to evaluate the glymphatic system in patients. ...
... However, it has been theorized that defective AQPs involved in cerebral fluid transport and glymphatic outflow may be dysfunctional in IIH, possibly due to hormonal or genetic alterations. 2 Likewise, AQP4 has been shown to regulate water transport between the brain and CSF, 5 and has also been shown to be differentially expressed in IIH. 21 Similarly, AQP1 has been implicated in drug-induced IIH. ...
Background and purpose:
The pathophysiology underlying idiopathic intracranial hypertension (IIH) remains incompletely understood. While one theory postulates impaired cerebral glymphatic clearance in IIH, there is a paucity of methods to quantify glymphatic activity in human brains. The purpose of this study was to use advanced diffusion-weighed imaging to evaluate the glymphatic clearance of IIH patients and how it may relate to clinical severity.
Materials and methods:
DWI was used to separately evaluate the diffusivity along the cerebral perivascular spaces and lateral association and projection fibers, with the degree of diffusivity used as a surrogate for glymphatic function (diffusion tensor image analysis along the perivascular space. Patients with IIH were compared with normal controls. Glymphatic clearance was correlated with several clinical metrics, including lumbar puncture opening pressure and Frisen papilledema grade (low grade: 0-2; high grade: 3-5).
Results:
In total, 99 patients with IIH were identified and compared with 6 healthy controls. Overall, patients with IIH had significantly lower glymphatic clearance based on DWI-derived diffusivity compared with controls (P = .005). Additionally, in patients with IIH, there was a significant association between declining glymphatic clearance and increasing Frisen papilledema grade (P = .046) but no correlation between opening pressure and glymphatic clearance (P = .27). Furthermore, healthy controls had significantly higher glymphatic clearance compared with patients with IIH and low-grade papilledema (P = .015) and high-grade papilledema (P = .002). Lastly, patients with IIH and high-grade papilledema had lower glymphatic clearance compared with patients with IIH and low-grade papilledema (P = .005).
Conclusions:
Patients with IIH possess impaired glymphatic clearance, which is directly related to the extent of clinical severity. The DWI-derived parameters can be used for clinical diagnosis or to assess response to treatment.
... [1,2,6] In addition, recent discoveries of the glymphatic and lymphatic systems of the brain may provide new insights into IIH. [7] In the brain, the glymphatic system, a fluid transport system that uses the perivascular network formed by astroglia cells, facilitates fluid clearance. [8] In contrast, the lymphatic system facilitates waste clearance and fluid drainage. ...
... [13,14] In addition, dilatation of the optic nerve sheaths was detected on coronal FLAIR (Fig. 3), a radiologic sign of IIH that may be explained by an overflow of the lymphatic CSF drainage pathway. [7] Time-of-flight magnetic resonance venography and angiography showed flow void signals of the bilateral transverse sinus (Fig. 4A) and normal cerebral arteries without any stenosis (Fig. 4B), respectively. Contrast-enhanced magnetic resonance venography was performed to verify the diagnosis of transverse sinus disorders. ...
... Some studies have revealed that the glymphatic system is involved in this process. [7,23] The glymphatic system is a brain-wide network for fluid transport and metabolic waste clearance that connects the cerebrovascular system and the CSF circulation, consisting of periarterial influx (glymphatic influx) of the subarachnoid CSF into the brain interstitium and the efflux of ISF with accompanying large-caliber veins. [24] The CSF in the subarachnoid spaces enters the periarterial spaces and is transported from the cortex toward the deep white matter along the arterioles. ...
Introduction:
Idiopathic intracranial hypertension (IIH) is a clinical syndrome characterized by increased intracranial pressure (ICP) without any identifiable cause. However, restrictions of cerebrospinal fluid absorption from the cerebral venous system, the glymphatic system overflow, and the cerebrospinal fluid's lymphatic pathways may be involved in the pathophysiology of IIH. Furthermore, an impaired glymphatic system is also implicated in the initiation and progression of cerebral small vessel disease (CSVD). Here, we reported a case of CSVD with concomitant IIH, possibly associated with the brain's glymphatic and lymphatic system dysfunction.
Case concern:
A 39-year-old male presented with worsening headaches over the bilateral parietal areas during the past year and nausea for 2 days. Fundus examination revealed bilateral papilledema and lumbar puncture suggestive of elevated ICP, laboratory results showed hyperhomocysteinemia and mutation of methylenetetrahydrofolate reductase C677T. On magnetic resonance imaging, subcortical small infarct, white matter lesions, lacunes, enlarged perivascular spaces and dilatation of the optic nerve sheaths was detected, and right transverse sinus stenosis and a hypoplastic left sinus were showed on contrast-enhanced magnetic resonance venography.
Diagnosis:
The diagnoses of IIH, CSVD, transverse sinus stenosis, and hyperhomocysteinemia were performed.
Intervision and outcomes:
The patient received antihypertensive, antiplatelet, anti-atherosclerotic, and homocysteine-lowering therapies. Finally, the patient's symptoms remised, and the increased ICP returned to normal; however, the bilateral TSS persisted after 3 months of follow-up.
Conclusions:
In this case, we speculate that the normal glymphatic outflow pathway may serve as a compensatory mechanism for regulating increased ICP in patients with bilateral venous sinus obstruction, indicating impaired venous outflow pathway, possibly associated with dysfunction of the glymphatic and lymphatic systems in patients with CSVD.
... AQP4, which occupies 50% of the surface area of capillary-facing end-feet, constitutes a low-resistance pathway for water movement between these compartments. AQP4 localized to astroglial end-feet around the microvasculature also has a role in draining the interstitial fluid (water and accompanying solute) efflux into the paravenous compartment [13][14][15]. ...
... This slow flow of CSF into the brain parenchyma induces a convective flow of interstitial fluid toward the perivenous spaces surrounding the large-caliber draining veins [13]. The drainage of the CSF from periarachnoid spaces and intraparenchymal perivenular spaces (together with interstitial fluid) will follow two pathways: the lymphatic outflow and the venous outflow pathways. ...
... The drainage of the CSF from periarachnoid spaces and intraparenchymal perivenular spaces (together with interstitial fluid) will follow two pathways: the lymphatic outflow and the venous outflow pathways. The interstitial cerebral fluid forms the glymphatic network, and finally drains in the sinus-associated lymphatics, but a fraction of the subarachnoid CSF also arrives in the dural sinus lymphatics [13,16]. ...
In this review, we provide an update on the pathogenesis, diagnosis, and management of adults with idiopathic intracranial hypertension (IIH) and implications of the cerebral venous system, highlighting the progress made during the past decade with regard to mechanisms of the venous outflow pathway and its connection with the cerebral glymphatic and lymphatic network in genesis of IIH. Early diagnosis and treatment are crucial for favorable visual outcomes and to avoid vision loss, but there is also a risk of overdiagnosis and misdiagnosis in many patients with IIH. We also present details about treatment of intracranial hypertension, which is possible in most cases with a combination of weight loss and drug treatments, but also in selected cases with surgical interventions such as optic nerve sheath fenestration, cerebral spinal fluid (CSF) diversion, or dural venous sinus stenting for some patients with cerebral venous sinus stenosis, after careful analysis of mechanisms of intracranial hypertension, patient clinical profile, and method risks.
... Although clear confirmation of this hypothesis has yet to be obtained, it is apparent that the dysfunctions of the various CSF drainage modes in IIH are neatly intertwined. 17 ...
... However, AGs may eventually cause mechanical obstruction of the venous sinuses as AGs increase, thus resulting in pressure elevation in the dural sinus and reduction in the efficiency of the venous CSF outflow pathway (Fig. 3). 17 Extrinsic stenosis is defined as the external compression of the venous sinuses by the adjacent brain parenchyma. Transverse venous sinuses are susceptible to extrinsic stenosis because of their potential to collapse in the setting of increased ICP. ...
... The original stenosis fades with the decrease in ICP after CSF removal. 17 Hence, extrinsic stenosis is not considered an independent cause of IIH. Sundararajan et al 34 demonstrated that most patients with IIH have extrinsic stenosis. ...
Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up‐to‐date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis.
Level of Evidence
1
Technical Efficacy Stage
2
... The following sites were rated by a reading radiologist (I.C., 4 years of experience): basal ganglia, centrum semiovale, and midbrain PVS. Briefly, basal ganglia and centrum semiovale PVS were rated 0 [none], 1 [1-10], 2 [11][12][13][14][15][16][17][18][19][20], 3 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], and 4 [>40], and midbrain PVS were rated 0 (nonvisible) or 1 (visible). Each hemisphere was evaluated separately for basal ganglia and centrum semiovale, and the highest score from either hemisphere was taken as the overall score. ...
... Lenck et al. have suggested that IIH might be related to glymphatic system overload (23). They hypothesized that overflow of the lymphatic CSF outflow pathway might result in venous restriction of CSF outflow. ...
Background
The impaired drainage of cerebrospinal fluid through the glymphatic system is thought to play a role in the idiopathic intracranial hypertension (IIH) pathophysiology. Limited data exist regarding the glymphatic system’s involvement in pediatric patients with IIH. Therefore, the study’s objective was to quantitatively evaluate alterations in parenchymal diffusivity and magnetic resonance imaging (MRI)-visible dilated perivascular spaces (PVS) as imaging indicators of glymphatic dysfunction in pediatric patients with IIH.
Methods
Patients diagnosed with IIH in 2017–2022 in a single tertiary center (Sheba Medical Center, Israel) were retrospectively reviewed. Twenty-four pediatric patients were enrolled. All patients underwent clinical 3-T brain MRI. The control group included 24 age- and gender-matched healthy subjects with a normal-appearing brain on imaging. We used automatic atlas-based diffusion-weighted imaging analysis to determine regional diffusivity of the thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, and brain stem. PVS were evaluated using a semi-quantitative rating scale on T2-weighted images. Variables were compared using the Mann-Whitney test. Multivariate analysis of covariance was used to test for differences between controls and IIH patients.
Results
No significant differences in regional brain diffusivity were observed between individuals with IIH and healthy controls (P=0.14–0.91 for various brain regions). The number of visible PVS was comparable between patients with IIH and the control group across all evaluated sites (P=0.12–0.74 for various brain regions).
Conclusions
Pediatric IIH patients exhibited similar patterns of parenchymal diffusivity and PVS compared to age-matched controls. These findings do not support the hypothesis that the glymphatic system may play a role in the pathophysiology of pediatric IIH, although previously postulated. However, employing more sophisticated magnetic resonance (MR) techniques could enhance the sensitivity in uncovering underlying glymphatic dysfunction. Further research is warranted to validate and explore this association in larger cohorts and investigate the underlying mechanisms involved in IIH.
... Based on these observations of physiological CSF circulation, Lenck et al. recently suggested a pathologic triad comprising the primary restriction of the venous CSF outflow pathway with secondary congestion of the glymphatic system and overflow of the lymphatic CSF outflow pathway to be responsible for the clinical manifestations of IIH [12]. ...
... These observations suggest an impaired clearance of brain tissue metabolites to the periphery in IIH patients, which is positively associated with lumbar puncture opening pressure elevation. This supports the recently evolving hypothesis concerning IIH pathogenesis comprising a pressure-dependent CSF outflow obstruction with secondary congestion of the glymphatic system [8,12]. ...
Abstract Background Impaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients. Methods NfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry. Results CSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p
... Se ha demostrado que las alteraciones del sueño, en especial el insomnio, pueden agravar la migraña 26 , facilitar la aparición de la DCP 27 y aumentar los niveles Aβ 28 . Estudios recientes demuestran que el flujo glinfático aumenta un 95% durante el En su artículo, Lenck, et al. postulan que estas «GA vasculares» podrían ser una continuación del espacio perivenoso y drenarían el LCR desde el SG hacia los senos venosos durales 38 . En consonancia con esto, sugieren que una disfunción de la vía de drenaje venoso produciría una sobrecarga de la vía de drenaje linfático, ocasionando una congestión del SG. ...
... Según estos autores, la disfunción microscópica del drenaje del LCR desde el SG perivenoso hacia los senos venosos durales produciría una estenosis intrínseca (por crecimiento del tamaño de la GA dentro del seno) y posteriormente, por aumento del volumen cerebral intersticial y compresión del seno transverso contra el cráneo, se produciría una estenosis extrínseca. Dichos procesos fisiopatológicos podrían explicar la mejoría transitoria y la posterior recidiva en los pacientes tratados con stent venoso 38 . ...
Resumen El sistema glinfático (SG) es una red en la que el líquido cefalorraquídeo fluye desde el espacio subaracnoideo hacia el intersticio cerebral a través del espacio perivascular, facilitada por la acuaporina 4 de la glía. Su principal función es la depuración de sustancias tóxicas y residuos proteicos, equivalente al sistema linfático de otros órganos. Duran-te la depresión cortical propagada se produce un colapso del SG, retrasando la depuración de sustancias proinfla-matorias y excitatorias, posiblemente originando una hiperexcitabilidad cortical localizada. Factores íntimamente rela-cionados con la migraña como el sueño, el alcohol, el ejercicio y el estrés, pueden afectar la función del SG. Adicionalmente, se ha postulado que una disfunción del drenaje perivenoso podría ser la clave detrás de la conges-tión del SG evidenciada en pacientes con hipertensión intracraneal idiopática. Palabras clave: Sistema glinfático. Líquido cefalorraquídeo. Migraña. Hipertensión intracraneal idiopática. Depuración. Abstract The glymphatic system (SG) is a network in which cerebrospinal fluid (CSF) flows from the subarachnoid space to the cerebral interstitium through the perivascular space, facilitated by aquaporin 4 from the glia. Its main function is the purification of toxic substances and protein residues, equivalent to the lymphatic system of other organs. During propagated cortical depression, SG collapses, delaying the clearance of proinflammatory and excitatory substances, possibly causing localized cortical hyperexcitability. Factors closely related to migraine such as sleep, alcohol, exercise and stress, can affect SG function. Additionally, it has been postulated that a perivenous drainage dysfunction could be the key behind the congestion of the SG evidenced in patients with idiopathic intracranial hypertension. INTRODUCCIÓN El sistema linfático drena el líquido intersticial y los residuos proteicos no eliminados en la circula-ción sanguínea por las vénulas poscapilares, y su función es crítica para mantener el equilibrio ho-meostásico e hidrostático en los tejidos vasculariza-dos 1. A pesar de su alta tasa metabólica y la alta sensibilidad a los cambios del ambiente extracelular, el cerebro en sí mismo carece de vasos linfáticos 2. Tradicionalmente se consideraba que los solu-tos intersticiales se eliminaban a través del líquido cefalorraquídeo (LCR) por medio de difusión simple; sin embargo, se ha demostrado que este sistema es ineficiente dado que la velocidad de depuración depende del tamaño del soluto. Así, mientras que la urea (60 Da) precisa 5,4 horas para trasladarse 1 cm, la albúmina (55,5 kDa) puede necesitar has-ta 109 horas 2,3. En cuanto a los residuos proteicos,
... The PSAS/ONSD ratio is then calculated (in this example, the ratio is 0.403). All measurements were completed between 10-12 mm posterior to the globe bral glymphatics resulting in altered CSF homeostasis, consequentially resulting in accumulation of interstitial fluid (ISF) with cerebral glymphedema and brain swelling [5][6][7][8][9]. However, it is unknown if dilation of the optic nerve in IIH is related to possible CSF dysregulation in patients with IIH. ...
Purpose
Idiopathic intracranial hypertension (IIH) is a complex neurological disease characterized by symptoms of raised intracranial pressure of unclear etiology. Although optic nerve sheath dilation is a common MR neuroimaging feature of IIH, how and why it occurs remains poorly understood. The purpose of the presented analysis was to investigate if optic nerve sheath dilation might be associated with neuroimaging correlates of cerebrospinal and interstitial fluid homeostasis.
Methods
IIH patients were retrospectively identified from 2016–2023 from our tertiary healthcare system. Brain MRIs were computationally segmented using FreeSurfer. Additionally, diffusion tensor imaging along the perivascular space (DTI-ALPS) was employed to assess cerebral glymphatic flow. The mean perioptic subarachnoid space (PSAS) to optic nerve sheath diameter (ONSD) ratio from both eyes was correlated with neuroimaging markers of CSF and interstitial fluid homeostasis (choroid plexus, ventricle, and gray and white matter volume) and glymphatic flow. All volumes of interest were normalized to total intracranial volume. Multiple linear regression was used to evaluate for associations between continuous variables accounting for covariates of patient age, sex, and body mass index.
Results
In total, 55 IIH patients (89% female; mean age: 30.3 years [SD: 7.6]) were included. Increasing PSAS/ONSD was found to be significantly associated with increasing normalized total choroid plexus volume (p = 0.001, R = 0.48) and total ventricle volume (P = 0.014, R = 0.39). Additionally, increasing PSAS/ONSD was associated with declining/worsening cerebral glymphatic clearance based on DTI-APLS (p = 0.043, R = 0.34). Additionally, there was a significant association between increasing PSAS/ONSD and increasing normalized total gray matter volume (p = 0.025, R = 0.36) and declining normalized total white matter volume (p = 0.012, R = 0.40).
Conclusion
These findings suggest that MR optic nerve sheath dilation in IIH might be associated with CSF dyshomeostasis with possible choroid plexus hyperplasia and impaired cerebral glymphatic flow based on DTI-ALPS. These findings encourage future research into the ocular glymphatic system in IIH patients.
... 9 It has been proposed that a glymphatic system overflow may occur in conditions of elevated intracranial pressure. 10 The hypothesis is that CSF may transude through the eye via the ocular glymphatic system in conditions of elevated intracranial pressure, akin to the noted phenomena in the nasal and ear cavities. ...
Background
Hemolacria, the excretion of blood-tinged tears, merges biological oddity with mysticism. This report discusses a unique case of hemolacria in a patient with possible idiopathic intracranial hypertension without papilledema (IIHWOP), resolving after acetazolamide treatment, exploring a potential pathogenic link.
Case Presentation
A 50-year-old male experienced daily hemolacria for three months along with occasional epistaxis and otorrhagia. He also suffered from chronic migraine, often accompanied with blurred vision and vertigo, and primary stabbing headache. Systemic and neurological assessments, along with computed tomography (CT) brain scans, ophthalmological and hematological tests revealed no underlying diseases. Brain magnetic resonance imaging (MRI) along with magnetic resonance venography, indicated left transverse sinus aplasia, bilateral ocular bulb flattening and enlargement of optic nerve sheaths, suggesting increased intracranial pressure. The patient began acetazolamide treatment. In the next three months, he experienced only four bleeding episodes and a dramatic reduction of monthly migraine days.
Discussion
Our report first associates hemolacria with possible IIHWOP, proposing a new pathogenic pathway. A derangement in the glymphatic system, implicated in idiopathic intracranial hypertension pathophysiology, could explain its ocular symptoms, including hemolacria. Our findings may contribute to understanding IIHWOP and the glympathic system's role in ocular physiology.
... A study by Lublinsky et al. revealed that AG counts were higher in IIH patients than in healthy individuals; however, this difference did not reach statistical significance (2.41 ± 1.12 vs. 1.50 ± 0.54, p = 0.096).81 Recent studies have suggested that AGs may not be as efficient as mature structures, which may represent fibrotic degeneration of the arachnoid villi.84 Furthermore, many individuals with normal CSF systems lack AGs, suggesting that their actual role in CSF drainage may be less significant than previously believed.85,86 ...
Background
Idiopathic intracranial hypertension (IIH) mainly affects obese young women, causing elevated intracranial pressure, headaches, and papilledema, risking vision loss and severe headaches. Despite weight loss as the primary treatment, the underlying mechanisms remain unclear. Recent research explores novel therapeutic targets.
Aims
This review aimed to provide a comprehensive understanding of IIH's pathophysiology and clinical features to inform pathogenesis and improve treatment strategies.
Methods
Recent publications on IIH were searched and summarized using PubMed, Web of Science, and MEDLINE.
Results
The review highlights potential pathomechanisms and therapeutic advances in IIH.
Conclusion
IIH incidence is rising, with growing evidence linking it to metabolic and hormonal disturbances. Early diagnosis and treatment remain challenging.
... Compression of the IJV has very important ramifications for CSF drainage and pressure and even causes a decline in cerebral perfusion (92)(93)(94). Under normal conditions, the majority of CSF fluid is absorbed by the subarachnoid granules and delivered via cerebral glymphatics and lymphatics to the epidural sinuses and then to the IJV (95)(96)(97). ...
We describe a yet to be reported phenomenon whereby the combination of a genetically vulnerable host and a chronic inflammatory state such as might occur from a chronic environmental toxic exposure leads to activation of mast cells and development of at least a localized hypermobility state including instability of anatomy in the craniofacio-cervical region. A cascade of events occurs from both the mast cell activation and unstable craniofacio-cervical structures that causes dysautonomia and hypopnea. These two phenomena lead to a large differential in daytime and nighttime blood carbon dioxide levels that cause an exaggerated increase in nighttime cerebral blood flow requiring rapid displacement of cerebrospinal fluid (CSF). The same unstable anatomy also prevents normal CSF and lymphatic drainage thereby causing an increase in intracranial pressure (the Spiky Phase). CSF pressure then pops-off through cranial nerve sheaths most notably through the olfactory nerve into sinus mucosa and into facial sinuses whereby it leaks out through the nose and ears, into facial tissue, or down the throat (the Leaky Phase). We call this Spiky-Leaky Syndrome and it may explain the vast collection of signs and symptoms co-segregating in these patients and also such other phenomena as cervical medullary syndrome, pseudotumor cerebri, idiopathic intracranial hypertension without papilledema, and occult tethered cord. Detailed data and theory are given as to why this has been difficult to detect to date as well as potential environmental toxins that may be responsible. Potential evaluations and therapies are posited
... The glymphatic theory describes how cardiac pulse-driven hydrostatic pressure drives the perivascular water through the brain parenchyma and how this water exchanges with interstitial fluid (ISF), picking up metabolites before traveling to the perivenous side [12]. This is facilitated by aquaporin-4 channels expressed on the astrocytic endfeet surrounding the brain vasculature [13]. Impairment of the glymphatic system can induce the accumulation of waste products in brain tissue. ...
Background: The glymphatic system removes neurodegenerative debris. The ocular glymphatic outflow is from the eye to the proximal optic nerve. In multiple sclerosis (MS), atrophy of the optic nerve increases the glymphatic outflow space. Here, we tested whether vitreous haze (VH) can provide novel insights into the relationship between neurodegeneration and the ocular glymphatic system in MS. Methods: This cross-sectional study comprised 315 persons with MS and 87 healthy controls (HCs). VH was quantified from optical coherence tomography (OCT) volume scans. Neurodegeneration was determined on three-dimensional T1 (3DT1) MRI, lesion detection on fluid-attenuated inversion (FLAIR), and layer thickness on OCT. Generalized estimating equations, corrected for age, were used to analyze associations between VH and metrics for neurodegeneration, demographics, and clinical scales. Group differences were determined between mild, moderate, and severe disability. Results: On the group level, VH scores were comparable between MS and control (p = 0.629). In MS, VH scores declined with disease duration (β = −0.009, p = 0.004) and age (β = −0.007, p = 0.001). There was no relation between VH scores and higher age in HCs. In MS patients, VH was related to normalized gray (NGMV, β = 0.001, p = 0.011) and white matter volume (NWMV, β = 0.001, p = 0.003), macular ganglion cell–inner plexiform layer thickness (mGCIPL, β = 0.006, p < 0.001), and peripapillary retinal nerve fiber layer thickness (pRNFL, β = 0.004, p = 0.008). VH was significantly lower in severe compared to mild disability (mean difference −28.86%, p = 0.058). Conclusions: There is a correlation between VH on OCT and disease duration, more severe disability and lower brain volumes in MS. Biologically, these relationships suggest accelerated glymphatic clearance with disease-related atrophy.
... Resistance in CSF venous or lymphatic outflow systems can disrupt CSF equilibrium [31•]. Glymphatic congestion may imply lymphatic outflow dysfunction [32]. The number and size of arachnoid granulations increase in patients with IIH, conceivably in response to elevated intracranial pressure. ...
Purpose of Review
Migraine and idiopathic intracranial hypertension (IIH) are increasingly encountered but remain enigmatic. This review compares the similarities and differences of the diagnostic criteria, pathophysiology, and risk factors for chronic migraine and IIH.
Recent Findings
While migraine and IIH are distinct diseases, both conditions are frequently found concurrently and may share a link. Increased intracranial pressure (ICP) in those with or without pre-existing migraine may present with migraine-like headaches and contribute to migraine chronification. Increased intracranial pressure may be a coincidental occurrence in patients with migraine and normalization of pressure does not always translate to headache improvement. Limited information is available regarding the standard of treatment for patients with chronic migraine and IIH without papilledema.
Summary
There continues to be controversy over the normal range of cerebral spinal fluid (CSF) values. Recognizing the concurrence of both conditions advances our understanding of headache pathology and demonstrates a striking need for more research.
... Internal jugular vein (IJV) stenosis may contribute to the pathophysiology of several neurological disorders, including idiopathic intracranial hypertension (IIH), Ménière disease, and transient monocular blindness [4,5,10,21]. Venous outflow compromise has been recognized as a key etiology of IIH [2,15,17]. Although the most common site for venous stenosis in IIH occurs at the transverse sigmoid junction, venous stenoses have been described elsewhere along the cerebral venous system [12,14]. ...
Background and objectives
Internal jugular vein (IJV) stenosis is associated with several neurological disorders including idiopathic intracranial hypertension (IIH) and pulsatile tinnitus. In cases of extreme bony compression causing stenosis in the infracondylar region, surgical decompression might be necessary. We aim to examine the safety and efficacy of surgical IJV decompression.
Methods
We retrospectively reviewed patients who received surgical IJV decompression via the extreme lateral infracondylar (ELI) approach between July 2020 and February 2022.
Results
Fourteen patients with IJV stenosis were identified, all with persistent headache and/or tinnitus. Six patients were diagnosed with IIH, three of whom failed previous treatment. Of the eight remaining patients, two failed previous treatment. All underwent surgical IJV decompression via styloidectomy, release of soft tissue, and removal of the C1 transverse process (TP). Follow-up imaging showed significant improvement of IJV stenosis in eleven patients and mild improvement in three. Eight patients had significant improvement in their presenting symptoms, and three had partial improvement. Two patients received IJV stenting after a lack of initial improvement. Two patients experienced cranial nerve paresis, and one developed a superficial wound infection.
Conclusion
The ELI approach for IJV decompression appears to be safe for patients who are not ideal endovascular candidates due to bony anatomy. Confirming long-term efficacy in relieving debilitating clinical symptoms requires longer follow-up and a larger patient cohort. Carefully selected patients with symptomatic bony IJV compression for whom there are no effective medical or endovascular options may benefit from surgical IJV decompression.
... La causa de esta estenosis no está esclarecida, y tampoco está definido si dicha estenosis es causa o consecuencia de la HEI, pero pudiera generar un aumento retrógrado en la presión venosa, lo cual a su vez disminuye el flujo de salida de LCR desde el sistema glinfático, concordando con el aumento de volumen mencionado anteriormente. Se desconoce el subtipo de acuaporina que media el transporte de agua entre el sistema glinfático y el seno venoso, sin embargo, todos los factores relacionados con la HEI (obesidad, sexo femenino, uso de ácido retinoico, etc.) también se han asociado con alteración de la expresión de diversos subtipos de acuaporina, lo cual pudiera jugar un rol importante en la patogénesis de la enfermedad 27 . ...
Resumen La teoría hidrodinámica del líquido cefalorraquídeo (LCR) postulada por Weed-Dandy-Cushing en el siglo XX propone la producción, circulación y reabsorción del líquido cefalorraquídeo en un sistema llamado la tercera circulación que simula el sistema circulatorio. Esta teoría muchas veces es insuficiente para explicar ciertos problemas clínicos específicos como la presencia de agenesia del Acueducto de Silvio en ausencia de hidrocefalia, la persistencia de LCR posterior a coagulación de plexos coroides, etc. Se describe la nueva hipótesis propuesta por Bulat Klarika Oreskovic que incluye más factores en la hidrodinamia, entendiendo que este sistema no escapa de las leyes biofísicas que rigen el resto del cuerpo humano, intentando explicar desde otro punto de vista los mismos fenómenos. Asimismo, ciertas patologías como la hidrocefalia normotensiva del adulto, hipertensión endocraneana Idiopática, entre otras, se explican mejor con estas teorías. El sistema glinfático (SG) se describe al margen de estas teorías como una vía por la cual a través del espacio perivascular el cerebro puede desechar ciertas sustancias nocivas que permite mantener la fisiología normal del Sistema Nervioso Central. El presente estudio intenta explicar de una manera sencilla dichas teorías y su relación con el SG y algunas patologías pertinentes. Palabras clave: Sistema glinfático, líquido cefalorraquídeo, hidrodinamia. Abstract The hydrodynamic theory of cerebrospinal fluid postulated (CSF) by Weed-Dandy-Cushing in the 20th century proposes the production, circulation and reabsorption of cerebrospinal fluid in a system called the third circulation that simulates the circulatory system. This theory is often insufficient to explain certain specific clinical problems such as the presence of agenesis of the aqueduct of Sylvius in the absence of hydrocephalus, the persistence of CSF after coagulation of the choroid plexus, etc. The new hypothesis proposed by Bulat Klarika Oreskovic is described, including more factors in hydrodynamics, understanding that this system does not escape from the biophysical laws that govern the rest of the human body, trying to explain from another point of view the same phenomena. Likewise, certain pathologies such as adult normal pressure hydrocephalus, idiopathic endocranial hypertension, among others, are better explained with this theory. The glymphatic system (GS) is described outside of these theories as a pathway through which the brain, through the perivascular space, can discard certain noxious substances that allow maintaining the normal physiology of the Central Nervous System. The present study attempts to explain in a simple way these theories and their relationship with the GS and some relevant pathologies.
... La causa de esta estenosis no está esclarecida, y tampoco está definido si dicha estenosis es causa o consecuencia de la HEI, pero pudiera generar un aumento retrógrado en la presión venosa, lo cual a su vez disminuye el flujo de salida de LCR desde el sistema glinfático, concordando con el aumento de volumen mencionado anteriormente. Se desconoce el subtipo de acuaporina que media el transporte de agua entre el sistema glinfático y el seno venoso, sin embargo, todos los factores relacionados con la HEI (obesidad, sexo femenino, uso de ácido retinoico, etc.) también se han asociado con alteración de la expresión de diversos subtipos de acuaporina, lo cual pudiera jugar un rol importante en la patogénesis de la enfermedad 27 . ...
La teoría hidrodinámica del líquido cefalorraquídeo (LCR) postulada por Weed-Dandy-Cushing en el siglo XX propone la producción, circulación y reabsorción del líquido cefalorraquídeo en un sistema llamado la tercera circulación que simula el sistema circulatorio. Esta teoría muchas veces es insuficiente para explicar ciertos problemas clínicos específicos como la presencia de agenesia del Acueducto de Silvio en ausencia de hidrocefalia, la persistencia de LCR posterior a coagulación de plexos coroides, etc. Se describe la nueva hipótesis propuesta por Bulat Klarika Oreskovic que incluye más factores en la hidrodinamia, entendiendo que este sistema no escapa de las leyes biofísicas que rigen el resto del cuerpo humano, intentando explicar desde otro punto de vista los mismos fenómenos. Asimismo, ciertas patologías como la hidrocefalia normotensiva del adulto, hipertensión endocraneana Idiopática, entre otras, se explican mejor con estas teorías. El sistema glinfático (SG) se describe al margen de estas teorías como una vía por la cual a través del espacio perivascular el cerebro puede desechar ciertas sustancias nocivas que permite mantener la fisiología normal del Sistema Nervioso Central. El presente estudio intenta explicar de una manera sencilla dichas teorías y su relación con el SG y algunas patologías pertinentes.
... There is however, an undeniable anatomic relationship between the CSF and the venous system, since the arachnoid villi represent the main pathway of resorption of CSF from the subarachnoid space into the lumen of the venous sinuses, and from there to the jugular vein and the general venous circulation (22). This connection, although anatomically feasible, can be expanded in several physiological hypotheses linking the CSF and interstitial fluid with the glymphatic, lymphatic and venous pathways of drainage with the development of IH (23), so it is theoretically possible that albeit no anatomic irregularities were found on MRI or CTA of the previous CSVT, there could be interstitial or venous alterations at the cellular level, warranting further research to understand this physiological relationship. ...
Trigeminal neuralgia, a chronic neuropathic pain, is characterized by frequent episodes of stabbing facial pain, in the territory of the trigeminal nerve, which can severely impair patient’s quality of life. It is primarily caused by vascular compression of the trigeminal nerve root, but it is sometimes secondary to other identifiable neurological conditions, such as multiple sclerosis or a cerebellopontine angle tumor. Uncommonly, it may be caused by the presence of idiopathic intracranial hypertension, a condition most likely identified by headache, visual disturbances, and sixth nerve palsy, among other manifestations. Secondary causes of trigeminal neuralgia are usually detected after an atypical clinical manifestation, such as ophthalmic rather than maxillary or mandibular nerve involvement, more than one branch affected, or bilateral symptoms. We present a patient who presented with trigeminal neuralgia as a primary manifestation, and after thorough evaluation she was diagnosed with intracranial hypertension as the underlying mechanism responsible of the trigeminal neuralgia.
... Genetic investigations involving AQP4, which facilitates the movement of water in and out of the brain, have not found any relationship with PTC [20]. Other potential factors to consider include mild inflammation and dysfunction within the glymphatic pathway [21]. In a recent study [18], we explored the role of viruses in the pathogenesis of PTC, but found no supporting evidence. ...
Pseudotumor cerebri (PTC) is a disorder characterized by increased intracranial pressure in the absence of a structural lesion or other identifiable cause. Cytokines, which are involved in the regulation of immune responses and inflammation, have been implicated in the pathogenesis of PTC. In a prospective, cross-sectional study at three centers in Israel, we analyzed cerebrospinal fluid (CSF) samples from 60 children aged 0.5–18 years, including 43 children with a definitive diagnosis of PTC and a control group of 17 children. Levels of IL-4, IL-10, IL-17, CCL2, CCL7, CCL8, CCL13, BDNF, and IFN-γ were measured using ELISA kits. Levels of CCL2 were significantly higher in the PTC group compared to the control group (p < 0.05), with no other significant differences in the measured cytokines between the two groups. The groups did not differ significantly in clinical presentation, imaging, treatment, or ophthalmic findings. Our findings provide preliminary evidence that CCL2 may be involved in the pathogenesis of PTC and may serve a potential target for therapy in PTC.
... It can be speculated whether impairment of the glymphatic system represents an additional pathophysiological basis for the development of aLPH. Meningeal lymphatic vessels have been shown to play a distinct role in patients suffering from SAH in a complex interaction of clearing erythrocytes from CSF to cervical lymph nodes, 24 re-entry of CSF, [25][26][27][28] and expression of aquaporin-4 at the blood-brain barrier and the blood-CSF interface, which is higher in patients suffering from SAH or IVH. [29][30][31][32][33] Sufficient CSF drainage potentially improves cerebral blood flow and normalizes the extracellular environment. ...
OBJECTIVE
Acute and chronic hydrocephalus are common pathologies after aneurysmal subarachnoid hemorrhage (SAH). Generally, the presence of acute hydrocephalus is associated with elevated intracranial pressure (ICP) treated with a ventricular drain. Subsequently, however, pronounced hydrocephalus without elevated ICP may develop in some patients with SAH in the postacute phase. This is described as acute low-pressure hydrocephalus (aLPH), and there are very limited data in the literature of this pathology. The aim of this study was to evaluate the rate of and factors associated with aLPH and describe its clinical course.
METHODS
In this retrospective single-center cohort study, the frequency and clinical characteristics of SAH-associated aLPH were investigated. Acute LPH was defined as an increase in ventricular size as measured by the Evans index, ICP within the normal range (< 5 mm Hg) at the time of ventricular enlargement, and timely neurological improvement after indwelling ventricular CSF drainage with negative pressure up to 5 cm H 2 O below normal level. Demographic and SAH-specific factors in patients with SAH treated using an external ventricular drain were extracted from the electronic medical chart and further analyzed.
RESULTS
From November 2010 to May 2020, 15 (3.7.%) of 406 patients with SAH fulfilled the criteria for aLPH. Acute LPH was diagnosed after an average of 13.1 ± 7.7 days. The presence of IVH and its extension were associated with the occurrence of aLPH. After undergoing the transient phase of aLPH, these patients subsequently developed a chronic, typical malresorptive hydrocephalus requiring a ventriculoperitoneal shunt more often (66.7% vs 17.4%, p < 0.001) and stayed longer in the intensive care unit (27 vs 20.5 days, p = 0.043) and in the hospital (36.4 vs 26.3 days, p = 0.004).
CONCLUSIONS
Acute LPH is a rare pathology in patients with SAH and negatively impacts the clinical course. It should be especially considered in patients with a lack of neurological improvement, an increase in ventricular width, and normal ICP values, so that forced CSF drainage is implemented.
... The high prevalence of obesity and the occurrence of PTC after administration of certain medications [19] might be explained by the effects of estrogen or retinoic acid on epithelial cells, leading to less CSF outflow. Genetic studies on AQP4, which facilitates water flow into and out of the brain, also found no association [17,20]. Other possibilities mentioned are low-grade inflammation and dysfunction in the glymphatic pathway [21]. ...
Pseudotumor cerebri (PTC) in children is a rare condition whose underlying cause remains largely unknown. No study has yet systematically examined viral infection as a cause of PTC. The current study aimed to characterize PTC in children and investigate the possible role of acute viral infection of the central nervous system in its pathogenesis. A prospective, cross-sectional study was conducted in three centers in Israel. Participants were 50 children aged 0.5–18 years, of whom 27 had a definitive diagnosis of pseudotumor cerebri (the study group) and 23 comprised a control. Data collected included clinical presentation, imaging, treatment, ophthalmic findings, and cerebrospinal fluid (CSF) analysis. Using the ALLPLEXTM meningitis panel, real-time polymerase chain reaction (PCR) was used to test for the presence of 12 common viruses. PTC patients (mean age 12 ± 4.3 years; 14 males, 13 females) had mean opening pressure of 41.9 ±10.2 mmH2O. All PTC patients had papilledema, and 25 (93%) had PTC symptoms. No viruses were found in the PTC group, while in the control group, one patient tested positive for Epstein–Barr virus and another for human herpesvirus type 6. Overall, in our study, PTC was not found to be associated with the presence of viruses in CSF.
... Intrinsic stenosis, on the other hand, occurs because of the growth of arachnoid granulations in the DVS or internal cephalocele due to the lack of permeability in the CSF-venous blood barrier. Therefore, TS stenosis can potentially contribute to the pathogenesis of IIH through complex mechanisms, and it has been suggested that clinical improvement in IIH in patients who have undergone TS stenting may also highlight the importance of this radiological finding [28]. ...
Background and PurposeThis study aimed to investigate the potential contribution of quantitative measurements of dural venous sinuses to the diagnosis of idiopathic intracranial hypertension (IIH) and the relationship between IIH and dural venous sinus dimensions on 3D post-gadolinium T1-weighted magnetic resonance (MR) images.Material and MethodsA total of 129 individuals (57 IIH patients and 72 controls) who complained of headache and underwent both magnetic resonance venography (MRV) and precontrast/postcontrast 3D T1-weighted MR imaging between 2018 and 2021 were included in this retrospective study. Dural venous sinus and jugular vein diameters were measured in all cases using post-gadolinium 3D T1 TFE images. The presence of transverse sinus (TS) hypoplasia and occipital sinus variation, the number and size of arachnoid granulations in the TS, and the presence of brain parenchymal herniation were also evaluated. Cut-off values that maximized accurate diagnosis of IIH were established on the receiver operating characteristic curve. The sensitivity and specificity of the diagnosis of IIH based on quantitative measurements of the dural sinus were calculated.ResultsThe ratios of the maximum to minimum TS diameters and the minimum TS diameters to minimum sigmoid sinus (SS) diameters were significantly higher in IIH patients than in the control group (p < 0.001). The diagnostic sensitivity and specificity values of TSmax/TSmin and TSmin sum/SSmin sum parameters for the detection of IIH were 84.2%, 84.7% and 83.3%, 84.2%, respectively.Conclusion
Practical measurements from multiplanar T1 sequences can be useful for both quantitative assessment and overcoming misinterpretation due to anatomical variation.
... 39 Some authors have postulated a role for glymphatic system dysfunction in the development of IIH. [40][41][42][43][44][45] One hypothesis is that transverse sinus stenoses play a role in the development of intracranial pressure by determining a decrease in the pressure gradient between the venous system and the subarachnoid space. 41,42 Different degrees of sinus stenoses would explain the different degrees of intracranial hypertension. ...
Pseudotumor cerebri is a syndrome that results from increased intracranial pressure. The main symptoms are headache, vision disturbances, and pulsatile tinnitus. Definitive diagnosis requires the presence of clinical and/or radiological signs of intracranial hypertension, high opening pressure on lumbar puncture (LP), and normal CSF constitution. Several studies have evaluated new contributions of CSF in the clinical evaluation and the in understanding of the pathophysiology of pseudotumor cerebri. Such studies have included the analysis of inflammatory biomarkers, adipokines, proteomic analysis, and CSF flow studies. In this review, we present the main results obtained so far and critically discuss the present status and the potential role of research involving the CSF in this condition. Based on current knowledge, it is possible to conclude that CSF research with new biomarkers has not yet provided information that can be employed in clinical practice at this moment. However, a better understanding of the constitution and dynamics of CSF circulation in patients with pseudotumor cerebri has brought some information about this condition and can potentially improve our knowledge about this condition in the future.
... The CNS is more difficult to define than peripheral systems regarding venous and lymphatic outflow. Approximately 500cc of CSF secreted by the choroid plexus is reabsorbed by arachnoid granulations (AG) and parenchymal lymphatic channels [60]. An AG is a protrusion of the arachnoid mater into the dural venous sinus that facilitates the reabsorption of CSF. ...
Subarachnoid hemorrhage (SAH) continues to be a leading cause of morbidity and mortality, with cerebral vasospasm as a common etiology of worse clinical progression. The purpose of this study was to evaluate and review the current literature concerning the effective treatment of SAH. The treatment options for SAH are expanding as new therapeutic targets are identified. Nimodipine is the primary medication prescribed due to its neuroprotective properties. In addition, certain drugs can enhance lymphatic flow and influence the recovery process, such as Dexmedetomidine, SSRIs, and DL-3-n-butylphthalide. Vasospastic and ischemic patients commonly undergo transluminal balloon angioplasty. Clinical trials have not yet provided conclusive evidence to support the use of magnesium or statins. Moreover, other agents such as calcium channel blockers, milrinone, hydrogen sulfide, exosomes, erythropoietin, cilostazol, fasudil, albumin, Eicosapentaenoic acid, corticosteroids, minocycline, and stellate ganglion blockade should be investigated further.
... Lenck et al. proposed that the development of IIH is driven by impaired interstitial flow from the glymphatic system to the dural venous sinuses, possibly by a dysfunction of an unknown subtype of aquaporin [80]. The authors hypothesise that this initial impairment is followed by congestion of the glymphatic system and subsequent overflow of the lymphatic outflow pathway. ...
This literature review discusses the potential significance of glymphatic system dysfunction to the pathophysiology of idiopathic intracranial hypertension (IIH). IIH is a clinical syndrome characterised by signs and symptoms which arise from raised intracranial pressure (ICP), in the absence of a clear primary cause of intracranial hypertension. The underlying pathophysiological mechanism driving IIH remains unclear and raised cerebrospinal fluid (CSF) secretion, reduced drainage, and elevated cerebral venous sinus pressure do not fully explain the condition’s aetiology. There is a growing literature that implicates the glymphatic system, a mechanism by which fluid moves into the brain parenchyma via periarterial channels and out via perivenous spaces and brain lymphatics, in IIH pathogenesis. We propose that aquaporin-4 (AQP4) changes, neurogliovascular unit disruption, a pro-inflammatory CSF profile and impaired glymphatic outflow are the main mechanisms driving glymphatic dysfunction in IIH. However, it remains unclear which of these mechanisms are primary causes and which are secondary effects. Further studies using CSF tracers, electron microscopy, and immunohistochemistry are needed to better evaluate the cellular and molecular pathology associated with IIH at different timepoints in the disease course, which will help elucidate the mechanistic role of the glymphatic system in the condition’s pathogenesis.
... Предполагается, что она способствует рециркуляции ЦСЖ по околососудистым пространствам, а также обеспечивает ее сообщение с интерстициальной жидкостью и дренаж ЦСЖ в лимфатическую систему через листки твердой Идиопатическая внутричерепная гипертензия: современный взгляд на проблему и трудности ранней диагностики мозговой оболочки [19]. Высказываются даже предположения о том, что не грануляции паутинной оболочки, а именно глимфатическая система обеспечивает основной механизм оттока ЦСЖ в норме [20]. Предполагают, что и ИВГ может быть обусловлена нарушением функции глимфатической системы из-за избыточного объема интерстициальной жидкости при ухудшении ее продвижения по околососудистым пространствам. ...
Идиопатическая внутричерепная гипертензия (ИВГ) – патология, которая проявляется синдромом повышенного внутричерепного давления (ВЧД) и обычно сопровождается билатеральным отеком зрительных нервов (ЗН). В статье представлен обзор актуальных данных по патогенезу и методам диагностики ИВГ. Увеличение числа случаев ИВГ, в том числе у лиц трудоспособного возраста, отсутствие детального понимания патогенеза заболевания, разнообразие вариантов его клинического течения, неспецифичность и другие ограничения в применении актуальных методов инструментальной диагностики ИВГ создают трудности в ранней постановке диагноза, выборе эффективного метода лечения и профилактике развития заболевания. Сохраняются трудности дифференциальной диагностики ИВГ с другими видами повышения ВЧД на начальных стадиях заболевания, и особенно при атипичном характере течения ИВГ. Становится актуальным междисциплинарный подход для поиска новых алгоритмов ранней диагностики ИВГ, выявления предикторов развития ИВГ, разработки диагностических инструментальных критериев. Это поможет открыть путь к пониманию звеньев патогенеза и разработать этиопатогенетически ориентированные методы профилактики и терапии ИВГ. Актуальна также разработка алгоритма диагностики и лечения пациентов с выявленным отеком ЗН, который обнаруживается в ходе рутинного офтальмологического осмотра. Ранняя диагностика ИВГ позволит уберечь пациента от необратимой утраты зрительных функций и развития тяжелых неврологических осложнений.
Idiopathic intracranial hypertension (IIH) manifests as a syndrome of increased intracranial pressure (ICP) and is usually accompanied by bilateral papilloedema. The article presents a review of current data on pathogenesis and diagnostic approaches to IIH. The increase in the number of cases of IIH, including people of working age, the lack of a detailed understanding of the disease pathogenesis, different variants of its clinical course, non- specificity and other limitations in the current instrumental methods of examination create difficulties in early IIH diagnosis, treatment and prevention. Difficulties persist in the differential diagnosis of IIH and other causes of increased ICP in the initial stages of the disease, especially in the atypical course of IIH. An interdisciplinary approach is relevant for creating new algorithms in early IIH diagnosis, predictors of disease development detection and developing of instrumental diagnostic criteria. This will help with understanding of IIH pathogenesis and with development of etiopathogenetically oriented methods of prevention and treatment of IIH. It is also relevant to develop an algorithm for the diagnosis and treatment of patients with identified papilloedema, which is detected during a routine ophthalmological examination. Early diagnosis of IIH may prevent irreversible vision loss and different severe neurological complications.
... The recently identified glymphatic system [49] and the CSF reabsorption occurring at cranial and spinal nerves levels significantly contribute to the overall interstitial fluid/CSF discharge [50]. Although quantitatively the reabsorption of CSF through the dural sinuses is no longer considered the more significant, the alternative CSF exit routes are probably easily saturable [51] and the glymphatic system may become inefficient in subjects with increased intracranial pressure [52]. On the contrary, the CSF discharge rate through arachnoid villi and granulations linearly correlates with the CSF/dural sinus transmural pressure gradient, up to values that exceed the CSF production rate by several times [53]. ...
Besides representing the place where a migraine attack generates, what is the physiological role of peptidergic control of arteriolar caliber within the trigemino-vascular system? Considering that the shared goal of most human CGRP-based neurosensory systems is the protection from an acute threat, especially if hypoxic, what is the end meaning of a migraine attack? In this paper, we have reviewed available evidence on the possible role of the trigemino-vascular system in maintaining cerebral perfusion pressure homeostasis, despite the large physiological fluctuations in intracranial pressure occurring in daily life activities. In this perspective, the migraine attack is presented as the response to a cerebral hypoxic threat consequent to a deranged intracranial pressure control aimed at generating a temporary withdrawal from the environment with limitation of physical activity, a condition required to promote the restoration of cerebral fluids dynamic balance.
... Meanwhile, in young subjects, the dural channels were relatively concentrated along the superior sagittal sinus, suggesting that aging may be associated with the evolution of the dural channels. Interestingly, arachnoid granulation, a fibrotic degeneration of the arachnoid villi (Lenck et al., 2018), has also shown development and evolution with aging. There is no arachnoid granulation at birth, and it first develops at the age of 18 months and spreads to other areas during the aging process (Mack et al., 2009). ...
Here, we report the existence of dural channels in the parasagittal dural space and dura mater in humans. Microscopic mapping was performed to observe dural channels and arachnoid granulations in the whole dural tissue of nine individuals, and ultrastructural examinations and 3D micro-CT were used for further identification. The dural channels were concentrated along the parasagittal dural space regardless of the distribution of arachnoid granulations. Microscopically, they varied in size, presenting as distorted round-shaped empty spaces resembling mature fat vacuoles without subcellular structures. We found them to be lacking in the expression of lymphatic and vascular markers. 3D micro-CT revealed Swiss-cheese-like structured empty spaces connected to each other. Our findings show that dural channels are part of the anatomical structure of the parasagittal dural and space and dura mater. Although they are not the meningeal lymphatic vessels themselves, dural channels may serve as a reservoir of cerebrospinal fluid drainage.
... The lymphatic pathway of intracranial CSF outflow is currently proposed as one of the factors involved in the pathogenesis of IIH. [15] Whereas, on the other hand, the presence of only the intracranial neuroimaging markers of IIH such as empty sella and venous flow disturbances may indicate a different pathogenetic mechanism of IIH in these two patients. Therefore, we hypothesize that a different pathogenetic mechanism may be the cause of the lack of response to mannitol in these two patients with IIH. ...
... Venous and lymphatic outflow in the CNS is not as well defined as in peripheral systems. However, the approximate 500 mL of CSF secreted by the choroid plexus has been shown to find reentry through arachnoid granulations (AG) and through parenchymal glymphatic channels [4,5]. AG are protrusions of the arachnoid mater into the dural venous sinus that facilitate CSF reabsorption via vesicular transport [6]. ...
The glymphatic system, or glial-lymphatic system, is a waste clearance system composed of perivascular channels formed by astrocytes that mediate the clearance of proteins and metabolites from the brain. These channels facilitate the movement of cerebrospinal fluid throughout brain parenchyma and are critical for homeostasis. Disruption of the glymphatic system leads to an accumulation of these waste products as well as increased interstitial fluid in the brain. These phenomena are also seen during and after subarachnoid hemorrhages (SAH), contributing to the brain damage seen after rupture of a major blood vessel. Herein this review provides an overview of the glymphatic system, its disruption during SAH, and its function in recovery following SAH. The review also outlines drugs which target the glymphatic system and may have therapeutic applications following SAH.
... Also, the transfer of CSF from the subarachnoid into the SSS only via the granulations may not be meet the turnover rate of the CSF. As an alternative to the direct CSF/SSS route, another means by which unusable and toxic metabolites derived from neural interstitial fluid exit the CSF is by their diffusion into the lymphatic vessels located in the dura (Fig. 1, B) [18]; these lymphatic vessels subsequently drain into the cervical lymph nodes [19]. Recently, a third option was morphologically defined in the human [20]. ...
The central nervous system (CNS) is endowed with a specialized cerebrospinal fluid (CSF)/lymph network which removes toxic molecules and metabolic by-products from the neural parenchyma; collectively, this has been named the glymphatic system. It allows CSF located in the subarachnoid space which surrounds the CNS to enter the depths of the brain and spinal cord by means of Virchow-Robin perivascular and perivenous spaces. CSF in the periarterial spaces is transferred across the astrocytic end feet which line these spaces aided by AQ4 channels; in the interstitium, the fluid moves via convection through the parenchyma to be eventually discharged into the perivenous spaces. As it passes through the neural tissue, the interstitial fluid flushes metabolic by-products and extracellular toxins and debris into the CSF of the perivenous spaces. The fluid then moves to the surface of the CNS where the contaminants are absorbed into true lymphatic vessels in the dura mater from where it is shunted out of the cranial vault to the cervical lymph nodes. Pineal melatonin released directly into the CSF causes the concentration of this molecule to be much higher in the CSF of the third ventricle than in the blood. After the ventricular melatonin enters the subarachnoid and Virchow-Robin spaces it is taken into the neural tissue where it functions as a potent antioxidant and anti-inflammatory agent. Experimental evidence indicates that it removes pathogenic toxins, e.g., amyloid-β and others, from the brain to protect against neurocognitive decline. Melatonin levels drop markedly during aging, coincident with the development of several neurodegenerative diseases and the accumulation of the associated neurotoxins.
Background
Endovascular stenting is a promising treatment for patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis (VSS). However, data on the impact of stenosis type on clinical outcomes of patients undergoing stenting treatment remain limited. This prospective cohort study aimed to compare post-stenting outcomes in patients with IIH and intrinsic versus extrinsic VSS.
Methods
Patients with IIH and VSS undergoing stenting at a tertiary hospital in China were enrolled consecutively from 2017 to 2023. Based on digital subtraction angiography, high-resolution MRI, and intravascular ultrasound findings, patients were categorized into two groups: intrinsic or extrinsic stenosis. At 6 months post-stenting, clinical outcomes including cerebrospinal fluid (CSF) pressure, headache, visual impairment, and papilledema were recorded. Multivariable regression models were used to explore the relationship between stenosis type and clinical outcomes.
Results
In total, 92 patients were included, 60 with intrinsic stenosis and 32 with extrinsic stenosis. At 6 months, the intrinsic group had lower CSF pressure (median 180 vs 210 mmH 2 O, β coefficient −31.8, 95% CI −54.0 to −9.6) and a higher rate of complete symptom resolution (81.7% vs 40.6%, OR 8.88, 95% CI 2.60 to 30.30) than the extrinsic group. Additionally, 36.8% (95% CI 10.5% to 77.2%) of the effect of stenosis type on complete symptom resolution at 6 months was mediated through reduction in CSF pressure.
Conclusion
This single-center study suggested that patients with IIH and intrinsic VSS had lower CSF pressure and better symptom recovery compared with those with extrinsic VSS at 6 months post-stenting. Further validation in other centers and populations is needed.
Trial registration number
ChiCTR.org.cn, ChiCTR-ONN-17010421.
Introduction
We aimed to explore the difference in choroidal vascular parameters using swept‐source optical coherence tomography (SS‐OCT) in patients with idiopathic intracranial hypertension (IIH) compared to controls. We also explored the ability of the choroidal parameters to reflect elevated intracranial pressure (ICP) in patients with IIH.
Methods
This observational study recruited patients diagnosed with IIH and healthy controls. A lumbar puncture was performed for ICP measurement. All the participants underwent OCT examinations. The choroid was automatically segmented and imaged by the OCT tool. The parafoveal choroidal vascular volume (CVV) and choroidal vascular index (CVI) were calculated in 3 mm annulus and 6 mm annulus.
Results
A total of 80 patients with IIH (34.67 ± 11.00 years; 37.50% males) and 92 controls (34.50 ± 12.08 years; 36.96% males) were included in the final analysis. Patients with IIH had higher BMI (< 0.001) and poor visual acuity (< 0.001) compared with controls. Patients with IIH demonstrated significantly lower parafovea CVI in both annuluses (p = 0.003 for 3 mm annulus, p = 0.001 for 6 mm annulus) compared to controls. Mean parafovea CVI in both annuluses was significantly correlated with ICP level (p = 0.014 for 3 mm annulus, p = 0.015 for 6 mm annulus). The combination of CVV and CVI in a 6 mm annulus demonstrated the highest diagnostic value with a mean AUC of 0.818.
Conclusion
CVI may serve as a potential marker for identifying IIH and reflecting ICP changes.
Neuroimaging is a paramount element for the diagnosis of idiopathic intracranial hypertension, a condition characterized by signs and symptoms of raised intracranial pressure without the identification of a mass or hydrocephalus being recognized. The primary purpose of this review is to deliver an overview of the spectrum and the specific role of the various imaging findings associated with the condition while providing imaging examples and educational concepts. Clinical perspectives and insights into the disease, including treatment options, will also be discussed.
Background
Spontaneous skull base cerebrospinal fluid leaks (CSFLs) are associated with increased intracranial pressure in idiopathic intracranial hypertension (IIH) and hypothesized to relate to skull base erosions due to increased CSF pressure. Given the increasing recognition of internal jugular venous stenosis (IJVS) as a cause of intracranial hypertension (IH), we evaluated the relationship between spinal CSFL and venous causes of IH.
Methods
The spinal CSFL database at a single institution was assessed to identify 12 consecutive spontaneous, non-traumatic spinal CSFL patients with CTV data. Exclusion criteria included documented IIH and iatrogenic CSFL. Demographics, clinical parameters, imaging characteristics, and IJV manometry results were recorded. Internal jugular venous stenosis was graded as: none (0–10%), mild (10–50%), moderate (50–80%), severe (>80–99%), and occluded (100%). Twelve consecutive patients who presented with cerebrovascular accidents without CSFL, matched by age and sex, were similarly analyzed as a control group. STROBE guidelines were used in reporting results.
Results
All CSFL patients had IJVS (83.3% bilateral, 33.3% severe) compared to 41.7% of the control group (33.3% bilateral, 16.7% severe-occluded); p = 0.04. All CSFL patients with available venogram manometry data had at least unilateral IJV gradients. Most patients presented with modified Rankin score (mRS) of 1 (66.7%), but in those with higher mRS, medical and/or surgical interventions were associated with decreased morbidity.
Conclusion
Spontaneous spinal CSFL was associated with IJVS in patients not meeting IIH criteria. Persistently high CSF pressure resulting in CSFL may cause opening pressure to be falsely normal or low. Internal jugular venous stenosis may be a viable target in recurrent CSFL management and improve morbidity.
Background
The pathophysiology of idiopathic intracranial hypertension (IIH) and other cerebral venous outflow disorders (CVD) has largely been unexplored. While a correlation between venous sinus pressure and opening pressure (OP) has been previously noted, there are limited data on this relationship in patients with prior venous sinus stenting (VSS).
Methods
A single center retrospective chart review was conducted on CVD patients who underwent diagnostic cerebral venography with manometry followed immediately by lateral decubitus lumbar puncture, from 2016 to 2024.
Results
206 patients underwent 216 total procedures and were included. Among all patients, there was a moderate nearly one-to-one correlation between OP and torcular or superior sagittal sinus (SSS) pressures. Thirty-two patients underwent testing after having undergone VSS. Patients with previous VSS showed a significantly altered relationship between venous pressures and OP, whereby as venous sinus pressures increased, OP increased more gradually in previously stented patients compared with non-stented patients. For example, when OP was fixed at 21 mm Hg and body mass index at 30 kg/m ² , predicted mean SSS pressure was 19.47 mm Hg in non-stented patients versus 16.91 mm Hg in stented patients.
Conclusion
This study confirmed a strong relationship between OP and venous sinus pressure in CVD patients. However, patients with previous VSS demonstrated an altered relationship with higher CSF pressures relative to venous pressures compared with naïve patients. This finding may have important clinical implications in the management of IIH patients.
In spite of expanding research, idiopathic intracranial hypertension (IIH) and its spectrum conditions remain challenging to treat. The failure to develop effective treatment strategies is largely due to poor agreement on a coherent disease pathogenesis model. Herein we provide a hypothesis of a unifying model centered around the internal jugular veins (IJV) to explain the development of IIH, which contends the following: (1) the IJV are prone to both physiological and pathological compression throughout their course, including compression near C1 and the styloid process, dynamic muscular/carotid compression from C3 to C6, and lymphatic compression; (2) severe dynamic IJV stenosis with developments of large cervical gradients is common in IIH-spectrum patients and significantly impacts intracranial venous and cerebrospinal fluid (CSF) pressures; (3) pre-existing IJV stenosis may be exacerbated by infectious/inflammatory etiologies that induce retromandibular cervical lymphatic hypertrophy; (4) extra-jugular venous collaterals dilate with chronic use but are insufficient resulting in impaired aggregate cerebral venous outflow; (5) poor IJV outflow initiates, or in conjunction with other factors, contributes to intracranial venous hypertension and congestion leading to higher CSF pressures and intracranial pressure (ICP); (6) glymphatic congestion occurs but is insufficient to compensate and this pathway becomes overwhelmed; and (7) elevated intracranial CSF pressures triggers extramural venous sinus stenosis in susceptible individuals that amplifies ICP elevation producing severe clinical manifestations. Future studies must focus on establishing norms for dynamic cerebral venous outflow and IJV physiology in the absence of disease so that we may better understand and define the diseased state.
The principles of cerebrospinal fluid (CSF) production, circulation and outflow and regulation of fluid volumes and pressures in the normal brain are summarised. Abnormalities in these aspects in intracranial hypertension, ventriculomegaly and hydrocephalus are discussed. The brain parenchyma has a cellular framework with interstitial fluid (ISF) in the intervening spaces. Framework stress and interstitial fluid pressure (ISFP) combined provide the total stress which, after allowing for gravity, normally equals intracerebral pressure (ICP) with gradients of total stress too small to measure. Fluid pressure may differ from ICP in the parenchyma and collapsed subarachnoid spaces when the parenchyma presses against the meninges. Fluid pressure gradients determine fluid movements. In adults, restricting CSF outflow from subarachnoid spaces produces intracranial hypertension which, when CSF volumes change very little, is called idiopathic intracranial hypertension (iIH). Raised ICP in iIH is accompanied by increased venous sinus pressure, though which is cause and which effect is unclear. In infants with growing skulls, restriction in outflow leads to increased head and CSF volumes. In adults, ventriculomegaly can arise due to cerebral atrophy or, in hydrocephalus, to obstructions to intracranial CSF flow. In non-communicating hydrocephalus, flow through or out of the ventricles is somehow obstructed, whereas in communicating hydrocephalus, the obstruction is somewhere between the cisterna magna and cranial sites of outflow. When normal outflow routes are obstructed, continued CSF production in the ventricles may be partially balanced by outflow through the parenchyma via an oedematous periventricular layer and perivascular spaces. In adults, secondary hydrocephalus with raised ICP results from obvious obstructions to flow. By contrast, with the more subtly obstructed flow seen in normal pressure hydrocephalus (NPH), fluid pressure must be reduced elsewhere, e.g. in some subarachnoid spaces. In idiopathic NPH, where ventriculomegaly is accompanied by gait disturbance, dementia and/or urinary incontinence, the functional deficits can sometimes be reversed by shunting or third ventriculostomy. Parenchymal shrinkage is irreversible in late stage hydrocephalus with cellular framework loss but may not occur in early stages, whether by exclusion of fluid or otherwise. Further studies that are needed to explain the development of hydrocephalus are outlined.
Background
Idiopathic intracranial hypertension (IIH) is a complex neurological condition characterized by symptoms of increased intracranial pressure of unclear etiology. While transverse sinus stenosis (TSS) is often present in patients with IIH, how and why it occurs remains unclear.
Methods
IIH patients and a set of age-matched normal controls were identified from our single-center tertiary care institution from 2016 to 2024. Brain MRIs before treatment were computationally segmented and parcellated using FreeSurfer software. Extent of TSS on MR venograms was graded using the Farb scoring system. Relationship between normalized brain volume, normalized brain-to-CSF volume, and TSS was investigated. Multiple linear regression was conducted to investigate the association between continuous variables, accounting for the covariates body mass index, sex, and age.
Results
In total, 84 IIH patients (mean age, 29.8 years; 87% female) and 15 normal controls (mean age, 28.1 years) were included. Overall, increasing/worsening TSS was found to be significantly associated with normalized total brain volume (p=0.018, R=0.179) and brain-to-CSF ratio volume (p=0.026, R=0.184). Additionally, there was a significant difference between controls and IIH patients with mild and severe stenosis regarding normalized total brain volume (ANCOVA, p=0.023) and brain-to-CSF ratio volume (ANCOVA, p=0.034). Likewise, IIH patients with severe TSS had a significantly higher brain-to-CSF volume compared with controls (p=0.038) and compared with IIH patients with mild TSS (p=0.038).
Conclusions
These findings suggest that total brain volume is associated with extent of TSS, which may reflect extramural venous compression due to enlarged brain and/or venous hypertension with associated cerebral congestion/swelling.
Introduction:
Pseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status.
Patients and methods:
We included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up.
Results:
We included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients.
Conclusion:
Prepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients.
Cerebrospinal fluid (CSF) flow patterns and their relationship with arterial pulsation can depict the function of glymphatic system (GS). We propose an improved multi-directional diffusion-sensitized driven-equilibrium (iMDDSDE) prepared heavily T2-weighted 3D FSE (iMDDSDE-HT2) magnetic resonance imaging (MRI) method to noninvasively assess the mobility (MO) of CSF distributed in the ventricles and perivascular spaces (PVS). This method could obtain 3D high resolution (1 mm isotropic) imaging of CSF MO with full brain coverage within five min and distinguish the CSF MO across different pulse phases using a peripheral pulse unit (PPU). The MO curves had the largest amplitude value in the PVS of middle cerebral artery (11.11 × 10 ⁻⁹ m 2/s ) and the largest amplitude growth rate in the posterior cerebral artery (189%). The average coefficient of variations (CVs) in non-pulse trigger and pulse phase 1 and 3 were 0.11, 0.10 and 0.09 respectively. The MO in older healthy participants was lower compared to the young participants, and the MO in cerebral major artery stenosis patients with acute ischemia stroke (AIS) were lower compared to those without AIS in several ventriclar ROIs (P < 0.05). This sequence is a clinically feasible method to effectively evaluate CSF flow patterns in human brain.
Background:
Venous sinus stenosis, typically at the junction of the transverse and sigmoid sinus, is increasingly recognized as a contributor to the pathophysiology of idiopathic intracranial hypertension (IIH), whether it be the intrinsic type that does not reverse with normalization of intracranial pressure or the extrinsic type, which does. Efforts to treat the stenosis and reduce the associated transstenotic gradient through placement of a stent at the site of stenosis have been studied over the past 2 decades, primarily through retrospective studies, with variable emphasis on formal visual testing and direct assessment of poststent opening pressure. Most studies have presented evidence for utilization of stenting as an alternative to cerebrospinal fluid shunting or optic nerve sheath fenestration in patients with IIH who harbor the stenosis and are refractory to or intolerant of intracranial pressure-lowering medications, but an assessment of the current data is needed to better understand the role of stenting for this patient population.
Evidence acquisition:
A search in PubMed was made for "IIH," "papilledema," and "venous stenting." Data pre and post stenting, including symptoms attributable to IIH, intracranial pressure, papilledema, retinal nerve fiber layer thickening on optical coherence tomography, and visual field assessment (mean deviation), were collected. Need for retreatment and complications were assessed among all studies. Studies using stenting for special circumstances, such as cerebrospinal leaks or for stenosis along anomalous vessels, were reviewed.
Results:
In total, 49 studies (45 retrospective and 4 prospective) and 18 case reports (with 3 or less patients) were found and included in the analysis, for a total of 1,626 patients. In 250 patients in whom poststent intracranial pressure was measured, the mean value was 19.7 cm H2O, reduced from a mean of 33 cm H2O. Transient visual obscurations resolved in 79.6% of 201 patients who complained of it, pulsatile tinnitus resolved in 84.7% of 515, diplopia resolved in 93% of 86 patients, and nonspecific visual symptoms such as "blurry vision" improved in 76.2% of 537 patients. Headaches resolved in 36% and improved in a further 40.7% of 1,105 patients in whom they were documented before stenting. Of 1,116 with papilledema, 40.8% demonstrated resolution and 38.2% improvement. The mean retinal nerve fiber layer thickness improved from 170.2 µm to 89.2 µm among 402 eyes in which optical coherence tomography was used to measure it. Among 135 eyes in which formal visual fields were performed pre and post stenting, the prestent average mean deviation of -7.35 dB improved to -4.72 dB after stenting. Complications associated with stenting included in-stent stenosis or thrombosis, subdural hematoma, intracerebral hematoma, cerebral edema, stent migration, and death. A recurrence of symptoms requiring a follow-up surgical intervention occurred in 9%.
Conclusions:
A growing body of evidence supports the use of venous sinus stenting as a viable option for medically refractory IIH, especially when papilledema threatens visual function. Complication and failure rates seem to be similar to alternative surgical approaches, although serious neurological sequalae can rarely occur. Emerging studies evaluating stent type, including novel stents designed for use in the venous system, may help improve ease of the procedure and long-term success rates. Prospective head-to-head studies are needed to better understand the performance of stenting compared with other interventions.
Background:
We aimed to assess the presence of sleep disturbances in adolescents with idiopathic intracranial hypertension (IIH) and to determine whether demographic, anthropometric, and clinical factors are associated with disrupted sleep.
Methods:
Sleep disturbances and patterns were evaluated in a cohort of adolescents (aged 12 to 18 years) with ongoing IIH and compared with a healthy age- and sex-matched control group. All participants responded to three self-rating questionnaires: the School Sleep Habits Survey (SSHS), the Pediatric Sleep Questionnaire (PSQ), and the Depression, Anxiety, and Stress Scale. The study group's demographic, clinical, laboratory, and radiological data were documented, and their association with sleep patterns was examined.
Results:
Thirty-three adolescents with ongoing IIH and 71 healthy controls were included. There was a significantly higher prevalence of sleep disturbances in the IIH group compared with the controls (SSHS, P < 0.001 and PSQ, P < 0.001), as well as of their independent subscales: sleep-related breathing disorders (P = 0.006), daytime sleepiness (P = 0.04), sleep/wake disruptions (P < 0.001), and sleep-related depressive tendencies (P < 0.001). According to subgroup analyses, these differences were also present between the normal-weight adolescents but not between the overweight IIH and control adolescents. No differences were found in the demographic, anthropometric, and IIH disease-related clinical measures between individuals with IIH with disrupted and normal sleep patterns.
Conclusions:
Sleep disturbances are common among adolescents with ongoing IIH, irrespective of their weight and disease-related characteristics. Screening adolescents with IIH for sleep disturbances is recommended as part of their multidisciplinary management.
The pathogenesis of idiopathic intracranial hypertension (IIH) is attributed to segmental stenosis of the venous sinus. The current treatment paradigm requires a trans-stenotic pressure gradient of ≥8 mmHg or ≥6 mmHg threshold. This study aimed to develop a machine learning screening method to identify patients with IIH using hemodynamic features. A total of 204 venous manometry instances (n = 142, training and validation; n = 62, test) from 135 patients were included. Radiomic features extracted from five arteriography perfusion parameter maps were selected using least absolute shrinkage and selection operator and then entered into support vector machine (SVM) classifiers. The Thr8-23-SVM classifier was created with 23 radiomic features to predict if the pressure gradient was ≥8 mmHg. On an independent test dataset, prediction sensitivity, specificity, accuracy, and AUC were 0.972, 0.846, 0.919, and 0.980, respectively (95% confidence interval: 0.980–1.000). For the 6 mmHg threshold, thr6-28-SVM incorporated 28 features, and its sensitivity, specificity, accuracy, and AUC were 0.923, 0.956, 0.935, and 0.969, respectively (95% confidence interval: 0.927–1.000). The trans-stenotic pressure gradient result was associated with perfusion pattern changes, and SVM classifiers trained with arteriography perfusion map-derived radiomic features could predict the 8 mmHg and 6 mmHg dichotomized trans-stenotic pressure gradients with favorable accuracy.
Some neurological disorders such as carotid cavernous fistulas and cerebral aneurysms have prominent ophthalmologic manifestations and are amenable to catheter-based neurointervention. Idiopathic intracranial hypertension is another disease for which neurointervention holds promise. Here we discuss the clinical presentation, imaging characteristics, and role of endovascular interventions in the management of the carotid-cavernous fistula and idiopathic intracranial hypertension and briefly discuss the ophthalmologic presentation of cerebral aneurysms.
In contrast to virtually all organ systems of the body, the central nervous system was until recently believed to be devoid of a lymphatic system. The demonstration of a complex system of paravascular channels formed by the endfeet of astroglial cells ultimately draining into the venous sinuses has radically changed this idea. The system is subsidized by the recirculation of cerebrospinal fluid (CSF) through the brain parenchyma along paravascular spaces (PVSs) and by exchanges with the interstitial fluid (IF). Aquaporin-4 channels are the chief transporters of water through these compartments. This article hypothesizes that glymphatic dysfunction is a major pathogenetic mechanism underpinning idiopathic intracranial hypertension (IIH). The rationale for the hypothesis springs from MRI studies, which have shown many signs related to IIH without evidence of overproduction of CSF. We propose that diffuse retention of IF is a direct consequence of an imbalance of glymphatic flow. This imbalance, in turn, may result from an augmented flow from the arterial PVS into the IF, by impaired outflow of the IF into the paravenous spaces, or both. Our hypothesis is supported by the facts that (i) visual loss, one of the main complications of IIH, is secondary to the impaired drainage of the optic nerve, a nerve richly surrounded by water channels and with a long extracranial course in its meningeal sheath; (ii) there is a high association between IIH and obesity, a condition related to paravascular inflammation and lymphatic disturbance, and (iii) glymphatic dysfunction has been related to the deposition of β-amyloid in Alzheimer’s disease. We conclude that the concept of glymphatic dysfunction provides a new perspective for understanding the pathophysiology of IIH; it may likewise entice the development of novel therapeutic approaches aiming at enhancing the flow between the CSF, the glymphatic system, and the dural sinuses.
Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases.
The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging.
Background:
Pseudotumor cerebri (PTC) is a condition characterized by symptoms and signs of increased intracranial pressure (ICP) with no intracranial mass or hydrocephalus, and with normal cerebrospinal fluid (CSF) composition. A variant of PTC known as "Normal Pressure Pseudotumor Cerebri" has the same features of PTC except for normal opening pressure.
Material and methods:
This is a series of 6 patients with typical symptoms and signs of increased ICP and normal neuroimaging but with normal CSF opening pressure. A second LP was done to re-measure the CSF opening pressure.
Results:
The mean age of the patients at diagnosis was 25 years (ranging from 19 to 31 years). All patients are females. All patients were obese with a mean body mass index (BMI) of 32.8 (ranging from 30 to 35). The mean duration of symptoms before presentation was 2.8 weeks (ranging from 1 to 8 weeks). The mean CSF opening pressure during the first LP was 11 cmH2O (ranging from 9 to 15 cmH2O). The CSF chemistry and culture of all patients were normal. The mean CSF opening pressure in the second LP was 7.3 cmH2O (ranging from 6 to 10 cmH2O). All patients were symptom free after one week of treatment, but the medications were continued till the complete disappearance of papilledema and the normalization of the visual field. The mean duration of treatment was 8 weeks (ranging from 5 to 12 weeks).
Conclusion:
Normal pressure PTC should be treated by medical treatment to avoid visual loss.
Unlabelled:
The glymphatic pathway expedites clearance of waste, including soluble amyloid β (Aβ) from the brain. Transport through this pathway is controlled by the brain's arousal level because, during sleep or anesthesia, the brain's interstitial space volume expands (compared with wakefulness), resulting in faster waste removal. Humans, as well as animals, exhibit different body postures during sleep, which may also affect waste removal. Therefore, not only the level of consciousness, but also body posture, might affect CSF-interstitial fluid (ISF) exchange efficiency. We used dynamic-contrast-enhanced MRI and kinetic modeling to quantify CSF-ISF exchange rates in anesthetized rodents' brains in supine, prone, or lateral positions. To validate the MRI data and to assess specifically the influence of body posture on clearance of Aβ, we used fluorescence microscopy and radioactive tracers, respectively. The analysis showed that glymphatic transport was most efficient in the lateral position compared with the supine or prone positions. In the prone position, in which the rat's head was in the most upright position (mimicking posture during the awake state), transport was characterized by "retention" of the tracer, slower clearance, and more CSF efflux along larger caliber cervical vessels. The optical imaging and radiotracer studies confirmed that glymphatic transport and Aβ clearance were superior in the lateral and supine positions. We propose that the most popular sleep posture (lateral) has evolved to optimize waste removal during sleep and that posture must be considered in diagnostic imaging procedures developed in the future to assess CSF-ISF transport in humans.
Significance statement:
The rodent brain removes waste better during sleep or anesthesia compared with the awake state. Animals exhibit different body posture during the awake and sleep states, which might affect the brain's waste removal efficiency. We investigated the influence of body posture on brainwide transport of inert tracers of anesthetized rodents. The major finding of our study was that waste, including Aβ, removal was most efficient in the lateral position (compared with the prone position), which mimics the natural resting/sleeping position of rodents. Although our finding awaits testing in humans, we speculate that the lateral position during sleep has advantage with regard to the removal of waste products including Aβ, because clinical studies have shown that sleep drives Aβ clearance from the brain.
The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.
© 2015 Aspelund et al.
One of the characteristics of the central nervous system is the lack of a classical lymphatic drainage system. Although it is now accepted that the central nervous system undergoes constant immune surveillance that takes place within the meningeal compartment, the mechanisms governing the entrance and exit of immune cells from the central nervous system remain poorly understood. In searching for T-cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the cerebrospinal fluid, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the central nervous system. The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.
Background
Many aspects of CSF dynamics are poorly understood due to the difficulties involved in quantification and visualization. In particular, there is debate surrounding the route of CSF drainage. Our aim was to quantify CSF flow, volume, and drainage route dynamics in vivo in young and aged spontaneously hypertensive rats (SHR) using a novel contrast-enhanced computed tomography (CT) method.
Methods
ICP was recorded in young (2–5 months) and aged (16 months) SHR. Contrast was administered into the lateral ventricles bilaterally and sequential CT imaging was used to visualize the entire intracranial CSF system and CSF drainage routes. A customized contrast decay software module was used to quantify CSF flow at multiple locations.
Results
ICP was significantly higher in aged rats than in young rats (11.52 ± 2.36 mmHg, versus 7.04 ± 2.89 mmHg, p = 0.03). Contrast was observed throughout the entire intracranial CSF system and was seen to enter the spinal canal and cross the cribriform plate into the olfactory mucosa within 9.1 ± 6.1 and 22.2 ± 7.1 minutes, respectively. No contrast was observed adjacent to the sagittal sinus. There were no significant differences between young and aged rats in either contrast distribution times or CSF flow rates. Mean flow rates (combined young and aged) were 3.0 ± 1.5 μL/min at the cerebral aqueduct; 3.5 ± 1.4 μL/min at the 3rd ventricle; and 2.8 ± 0.9 μL/min at the 4th ventricle. Intracranial CSF volumes (and as percentage total brain volume) were 204 ± 97 μL (8.8 ± 4.3%) in the young and 275 ± 35 μL (10.8 ± 1.9%) in the aged animals (NS).
Conclusions
We have demonstrated a contrast-enhanced CT technique for measuring and visualising CSF dynamics in vivo. These results indicate substantial drainage of CSF via spinal and olfactory routes, but there was little evidence of drainage via sagittal sinus arachnoid granulations in either young or aged animals. The data suggests that spinal and olfactory routes are the primary routes of CSF drainage and that sagittal sinus arachnoid granulations play a minor role, even in aged rats with higher ICP.
Background and purpose:
Impaired CSF homeostasis and altered venous hemodynamics are proposed mechanisms for elevated pressure in IIH. However, the lack of ventricular expansion steered the focus away from CSF homeostasis in IIH. This study aims to measure intracranial CSF volumes and cerebral venous drainage with MR imaging to determine whether increased CSF volume from impaired CSF homeostasis and venous hemodynamics occur in obesity-related IIH.
Materials and methods:
Two homogeneous cohorts of 11 newly diagnosed pretreatment overweight women with IIH and 11 overweight healthy women were prospectively studied. 3D volumetric MR imaging of the brain was used to quantify CSF and brain tissue volumes, and dynamic phase contrast was used to measure relative cerebral drainage through the internal jugular veins.
Results:
Findings confirm normal ventricular volume in IIH. However, extraventricular CSF volume is significantly increased in IIH (290 ± 52 versus 220 ± 24 mL, P = .001). This is even more significant after normalization with intracranial volume (P = .0007). GM interstitial fluid volume is also increased in IIH (602 ± 57 versus 557 ± 31 mL, P = .037). Total arterial inflow is normal, but relative venous drainage through the IJV is significantly reduced in IIH (65 ± 7% versus 81 ± 10%, P = .001).
Conclusions:
Increased intracranial CSF volume that accumulates in the extraventricular subarachnoid space provides direct evidence for impaired CSF homeostasis in obesity-associated IIH. The finding of larger GM interstitial fluid volume is consistent with increased overall resistance to cerebral venous drainage, as evident from reduced relative cerebral drainage through the IJV. The present study confirms that both impaired CSF homeostasis and venous hemodynamics coexist in obesity-associated IIH.
There are no conventional lymphatics in the brain but physiological studies have revealed a substantial and immunologically significant lymphatic drainage from brain to cervical lymph nodes. Cerebrospinal fluid drains via the cribriform plate and nasal mucosa to cervical lymph nodes in rats and sheep and to a lesser extent in humans. More significant for a range of human neurological disorders is the lymphatic drainage of interstitial fluid (ISF) and solutes from brain parenchyma along capillary and artery walls. Tracers injected into grey matter, drain out of the brain along basement membranes in the walls of capillaries and cerebral arteries. Lymphatic drainage of antigens from the brain by this route may play a significant role in the immune response in virus infections, experimental autoimmune encephalomyelitis and multiple sclerosis. Neither antigen-presenting cells nor lymphocytes drain to lymph nodes by the perivascular route and this may be a factor in immunological privilege of the brain. Vessel pulsations appear to be the driving force for the lymphatic drainage along artery walls, and as vessels stiffen with age, amyloid peptides deposit in the drainage pathways as cerebral amyloid angiopathy (CAA). Blockage of lymphatic drainage of ISF and solutes from the brain by CAA may result in loss of homeostasis of the neuronal environment that may contribute to neuronal malfunction and dementia. Facilitating perivascular lymphatic drainage of amyloid-beta (Abeta) in the elderly may prevent the accumulation of Abeta in the brain, maintain homeostasis and provide a therapeutic strategy to help avert cognitive decline in Alzheimer's disease.
We studied the anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé in 57 consecutive angiograms. Patients with pathology in intracranial venous structures or with inadequate image quality of the venous system were excluded. Arachnoid granulations were found in 12 of the 57 patients (21.1%), always at the junction of the vein of Labbé and the transverse sinus; the vein of Labbé was present in 55 patients (96.5%), most often without associated arachnoid granulations; the latter, however, were not observed in the absence of a vein of Labbé. This study confirms the close, constant anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbé. This observation may help to differentiate arachnoid granulations from pathologic conditions involving the transverse sinus such as dural sinus thrombosis. The constant character of this relationship suggests a developmental role of afferent veins in the formation of arachnoid granulations.
Background
There is limited information regarding the effects of spaceflight on the anatomical configuration of the brain and on cerebrospinal fluid (CSF) spaces.
Methods
We used magnetic resonance imaging (MRI) to compare images of 18 astronauts’ brains before and after missions of long duration, involving stays on the International Space Station, and of 16 astronauts’ brains before and after missions of short duration, involving participation in the Space Shuttle Program. Images were interpreted by readers who were unaware of the flight duration. We also generated paired preflight and postflight MRI cine clips derived from high-resolution, three-dimensional imaging of 12 astronauts after long-duration flights and from 6 astronauts after short-duration flights in order to assess the extent of narrowing of CSF spaces and the displacement of brain structures. We also compared preflight ventricular volumes with postflight ventricular volumes by means of an automated analysis of T1-weighted MRIs. The main prespecified analyses focused on the change in the volume of the central sulcus, the change in the volume of CSF spaces at the vertex, and vertical displacement of the brain.
Results
Narrowing of the central sulcus occurred in 17 of 18 astronauts after long-duration flights (mean flight time, 164.8 days) and in 3 of 16 astronauts after short-duration flights (mean flight time, 13.6 days) (P<0.001). Cine clips from a subgroup of astronauts showed an upward shift of the brain after all long-duration flights (12 astronauts) but not after short-duration flights (6 astronauts) and narrowing of CSF spaces at the vertex after all long-duration flights (12 astronauts) and in 1 of 6 astronauts after short-duration flights. Three astronauts in the long-duration group had optic-disk edema, and all 3 had narrowing of the central sulcus. A cine clip was available for 1 of these 3 astronauts, and the cine clip showed upward shift of the brain.
Conclusions
Narrowing of the central sulcus, upward shift of the brain, and narrowing of CSF spaces at the vertex occurred frequently and predominantly in astronauts after long-duration flights. Further investigation, including repeated postflight imaging conducted after some time on Earth, is required to determine the duration and clinical significance of these changes. (Funded by the National Aeronautics and Space Administration.)
Obesity is one of the most important metabolic disorders of this century and is associated with a cluster of the most dangerous cardiovascular disease risk factors, such as insulin resistance and diabetes
, dyslipidemia and hypertension
, collectively named Metabolic Syndrome. The role of aquaporins in glycerol
metabolism
facilitating glycerol release from the adipose tissue and distribution to various tissues and organs, unveils these membrane channels as important players in lipid balance and energy homeostasis and points to their involvement in a variety of pathophysiological mechanisms including insulin resistance, obesity and diabetes.
This review summarizes the physiologic role of aquaglyceroporins
in glycerol
metabolism
and lipid homeostasis, describing their specific tissue distribution, their involvement in glycerol balance and their implication in obesity and fat-related metabolic complications. The development of specify pharmacologic modulators able to regulate aquaglyceroporins
expression
and function
, in particular AQP7 in adipose tissue, might constitute a novel approach for controlling obesity and other metabolic disorders.
Key points:
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.
Abstract:
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission-critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1 year. ICP was assessed by placing a fluid-filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6 deg head-down tilt bedrest). ICP was lower when seated in the 90 deg upright posture compared to lying supine (seated, 4 ± 1 vs. supine, 15 ± 2 mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7 ± 3 vs. microgravity, 4 ± 2 mmHg) and ICP (supine, 17 ± 2 vs. microgravity, 13 ± 2 mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90 deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15 ± 2 vs. 24 h head-down tilt, 15 ± 4 mmHg). Complete removal of gravity does not pathologically elevate ICP but does prevent the normal lowering of ICP when upright. These findings suggest the human brain is protected by the daily circadian cycles in regional ICPs, without which pathology may occur.
Magnetic resonance imaging (MRI) signs of elevated intracranial pressure and idiopathic intracranial hypertension have been well characterized in adults but not in children. The MRIs of 50 children with idiopathic intracranial hypertension and 46 adults with idiopathic intracranial hypertension were reviewed for optic nerve head protrusion, optic nerve head enhancement, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, empty or partially empty sella, tonsillar herniation, enlargement of Meckel’s cave meningoceles, and transverse venous sinus stenosis(TSS). Compared to adolescents (11-17 years, n = 40) and adults (>17 years, n = 46), prepubescent children (<11 years, n = 10) had lower frequencies of scleral flattening (50% vs 89% and 85%, P = .02), increased perioptic cerebrospinal fluid (60% vs 84% and 89%, P = .08), optic nerve tortuosity (20% vs 46% and 59%, P = .07), empty or partially empty sella (56% vs 78% and 93%, P = .007), and TSS (67% vs 93% and 96%, P = .04). Children with idiopathic intracranial hypertension have similar MRI findings as adults, but they are less frequent in prepubescent children.
Background:
Over the past decade, stenting of lateral sinus stenosis has been used to treat idiopathic intracranial hypertension. Two types of stenoses have been identified: extrinsic and intrinsic.
Objective:
The aim of this study was to report the results of our use of this procedure to treat patients with extrinsic or intrinsic stenoses in idiopathic intracranial hypertension.
Methods:
We retrospectively studied clinical, radiological, and manometric data from patients with idiopathic intracranial hypertension who were treated at our institution between January 2009 and January 2015 by stenting of the lateral sinus.
Results:
Data were studied from 19 women and 2 men. Average body mass index was 29 kg/m 2 , and the median age at stenting was 33 years. Patients with extrinsic stenoses were younger than those with intrinsic stenoses. Transstenotic gradients measured with patients under general anesthesia were lower than those measured with patients under local anesthesia. In all cases, stenting was effective for papilledema and pulsatile tinnitus. Seventeen patients reporting headaches found that they disappeared completely after stenting. Two complications without long-term effects were reported.
Conclusion:
Irrespective of the type of stenosis, stenting of lateral sinus stenoses is an effective treatment for intracranial hypertension symptoms. At our institution, this treatment has replaced draining of cerebrospinal fluid when treatment with acetazolamide has proved to be ineffective.
Background:
The primary role of brain imaging in idiopathic intracranial hypertension (IIH) is to exclude other pathologies causing intracranial hypertension. However, subtle radiologic findings suggestive of IIH have emerged with modern neuroimaging. This review provides a detailed description of the imaging findings reported in IIH and discusses their possible roles in the pathophysiology and the diagnosis of IIH.
Evidence acquisition:
References were identified by searches of PubMed from 1955 to January 2015, with the terms "idiopathic intracranial hypertension," "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," "magnetic resonance imaging," "magnetic resonance venography," "computed tomography (CT)," "CT venography," "imaging," and "cerebrospinal fluid (CSF) leak." Additional references were identified by hand search of relevant articles. When possible, we extracted the number of patients and control subjects from each study for each radiological finding. When at least 2 studies used the same criteria to define a radiological finding, all patients from these studies were pooled to obtain a mean sensitivity and specificity with 95% confidence interval.
Results:
Specific neuroimaging findings may suggest long-standing IIH, including empty sella, flattening of the posterior globes, optic nerve head protrusion, distention of the optic nerve sheaths, tortuosity of the optic nerve, cerebellar tonsillar herniation, meningoceles, CSF leaks, and transverse venous sinus stenosis.
Conclusion:
Although IIH remains a diagnosis of exclusion, the most recently proposed diagnostic criteria have included neuroimaging findings to suggest IIH when major diagnostic criteria are not fulfilled. However, these findings are not diagnostic of IIH, and their presence is not required for the diagnosis of definite IIH. Their incidental discovery on brain imaging should not prompt invasive procedures, unless other signs of IIH, such as papilledema, are present.
Although the peripheral lymphatic system performs such essential physiological functions as interstitial fluid (ISF) and protein homeostasis and immune surveillance, the apparent absence of conventional lymphatic vessels from the central nervous system (CNS) has remained a persistent mystery of neuroscience, particularly in light of neural cells’ exquisite sensitivity to the composition of their extracellular environment.
Objective:
In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain.
Methods:
CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence.
Results:
Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange.
Interpretation:
We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates.
Objective:
MRI abnormalities have been described in patients with increased intracranial pressure (ICP), including in those with idiopathic intracranial hypertension (IIH). Spontaneous CSF-filled outpouchings of the dura (meningoceles) and secondary CSF leaks can occur from elevated ICP in patients with IIH; however, few studies have evaluated these findings. Our objective was to evaluate the frequency of spontaneous intracranial meningoceles among IIH patients and determine their association with visual outcome.
Materials and methods:
We performed a retrospective case-control study of consecutive IIH patients between 2000 and 2011 who underwent MRI that included T2-weighted imaging. Demographics, presenting symptoms, CSF opening pressure, and visual outcome were collected for the first and last evaluations. Control subjects included patients without headache or visual complaints who had normal brain MRI results. Stratified analysis was used to control for potential confounding by age, sex, race, and body mass index.
Results:
We included 79 IIH patients and 76 control subjects. Meningoceles were found in 11% of IIH patients versus 0% of control subjects (p<0.003). Prominent Meckel caves without frank meningoceles were found in 9% of IIH patients versus 0% of control subjects (p<0.003). Among IIH patients, the presence of meningocele or prominent Meckel caves was not associated with demographics, symptoms, degree of papilledema, CSF opening pressure, visual acuity, or visual field defect severity.
Conclusion:
Meningoceles are significantly more common in IIH patients than in control subjects and can be considered an additional imaging sign for IIH. Meningoceles are not, however, associated with decreased CSF opening pressure or better visual outcome in IIH.
Idiopathic intracranial hypertension (IIH) is increasingly recognized as a cause of spontaneous cerebrospinal fluid (CSF) leak in the otolarnygological and neurosurgical literature. The diagnosis of IIH in patients with spontaneous CSF leaks typically is made a few weeks after surgical repair of the leak when symptoms and signs of elevated intracranial pressure (ICP) appear.
Case reports and literature review. Two young obese women developed spontaneous CSF rhinorrhea related to an empty sella in one and a cribriform plate encephalocele in the other. Both patients underwent surgical repair of the CSF leak. A few weeks later, they developed chronic headaches and bilateral papilledema. Lumbar punctures showed elevated CSF opening pressures with normal CSF contents, with temporary improvement of headaches. A man with a 3-year history of untreated IIH developed spontaneous CSF rhinorrhea. He experienced improvement of his headaches and papilledema after a CSF shunting procedure, and the rhinorrhea resolved after endoscopic repair of the leak.
These cases and the literature review confirm a definite association between IIH and spontaneous CSF leak based on: 1) similar demographics; 2) increased ICP in some patients with spontaneous CSF leak after leak repair; 3) higher rate of leak recurrence in patients with raised ICP; 4) patients with intracranial hypertension secondary to tumors may develop CSF leak, confirming that raised ICP from other causes than IIH can cause CSF leak.
CSF leak occasionally may keep IIH patients symptom-free; however, classic symptoms and signs of intracranial hypertension may develop after a CSF leak is repaired, exposing these patients to a high risk of recurrence of the leak unless an ICP-lowering intervention is performed.
Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.
Idiopathic intracranial hypertension (IIH) is a clinical disorder of unknown etiology manifesting with increased intracranial pressure in the absence of hydrocephalus, an underlying mass lesion, and demonstrating normal cerebrospinal fluid composition. IIH may exhibit several non-specific imaging findings including: an empty sella, posterior globe flattening, tortuosity of the optic nerve, and optic nerve sheath distention.
To introduce widening of the foramen ovale as a new imaging marker for IIH.
IIH is a syndrome which may exhibit several previously described non-specific imaging findings including: an empty sella, posterior globe flattening, tortuosity of the optic nerve, and optic nerve sheath distention. We hypothesize that chronically elevated cerebrospinal fluid pressure can lead to osseous erosions and we propose widening of the foramen ovale as a new imaging marker for IIH.
Average foramen ovale sizes were increased in patients with IIH compared to controls (30.03 ± 7.00 mm(2) vs. 24.21 ± 5.97 mm(2), P < 0.001). For a cut-off value of 30 mm(2), the sensitivity of FO area to detect IIH was 50%, with 81% specificity. Classic findings were significantly more common in patients with IIH compared to controls including: empty sella (65.9% vs. 0%), posterior globe flattening (65.9% vs. 4.5%), vertical tortuosity of the optic nerve (54.5% vs. 9.1%), and optic nerve sheath distention (52.3% vs. 11.4%, all P values < 0.001).
Our study confirms the association of several classic imaging findings with IIH and supports widening of the foramen ovale as an additional imaging marker which may be incorporated into the evaluation of patients suspected to have this condition.
To investigate the accuracy of individual and combinations of signs on brain magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) in the diagnosis of idiopathic intracranial hypertension (IIH).
This study was approved by the institutional research ethics board without informed consent. Forty-three patients and 43 control subjects were retrospectively identified. Each patient and control had undergone brain MRI and MRV. Images were anonymized and reviewed by three neuroradiologists, blinded to clinical data, for the presence or absence of findings associated with IIH. The severity of stenosis in each transverse sinus was graded and summed to generate a combined stenosis score (CSS). The sensitivity, specificity, and likelihood ratios (LR) were calculated for individual and combinations of signs.
Partially empty sella (specificity 95.3%, p < 0.0001), flattening of the posterior globes (specificity 100%, p < 0.0001), and CSS <4 (specificity 100%, p < 0.0001) were highly specific for IIH. The presence of one sign, or any combination, significantly increased the odds of a diagnosis of IIH (LR+ 18.5 to 46, p < 0.0001). Their absence, however, did not rule out IIH.
Brain MRI with venography significantly increased the diagnostic certainty for IIH if there was no evidence of a mass, hydrocephalus, or sinus thrombosis and one of the following signs was present: flattening of the posterior globes, partially empty sella, CSS <4. However, absence of these signs did not exclude a diagnosis of IIH.
The use of unilateral dural sinus stent placement in patients with idiopathic intracranial hypertension (IIH) has been described by multiple investigators. To date there is a paucity of information on the angiographic and hemodynamic outcome of these procedures. The object of this study was to define the clinical, angiographic, and hemodynamic outcome of placement of unilateral dural sinus stents to treat intracranial venous hypertension in a subgroup of patients meeting the diagnostic criteria for IIH.
Eighteen consecutive patients with a clinical diagnosis of IIH were treated with unilateral stent placement in the transverse-sigmoid junction region. All patients had papilledema. All 12 female patients had headaches; 1 of 6 males had headaches previously that disappeared after weight loss. Seventeen patients had elevated opening pressures at lumbar puncture. Twelve patients had opening pressures of 33-55 cm H(2)O. All patients underwent diagnostic cerebral arteriography that showed venous outflow compromise by filling defects in the transverse-sigmoid junction region. All patients underwent intracranial selective venous pressure measurements across the filling defects. Follow-up arteriography was performed in 16 patients and follow-up venography/venous pressure measurements were performed in 15 patients.
Initial pressure gradients across the filling defects ranged from 10.5 to 39 mm Hg. Nineteen stent procedures were performed in 18 patients. One patient underwent repeat stent placement for hemodynamic failure. Pressure gradients were reduced in every instance and ranged from 0 to 7 mm Hg after stenting. Fifteen of 16 patients in whom ophthalmological follow-up was performed experienced disappearance of papilledema. Follow-up arteriography in 16 patients at 5-99 months (mean 25.3 months, median 18.5 months) showed patency of all stents without in-stent restenosis. Two patients had filling defects immediately above the stent. Four other patients developed transverse sinus narrowing above the stent without filling defects. One of these patients underwent repeat stent placement because of hemodynamic deterioration. Two of the other 3 patients had hemodynamic deterioration with recurrent pressure gradients of 10.5 and 18 mm Hg.
All stents remained patent without restenosis. Stent placement is durable and successfully eliminates papilledema in appropriately selected patients. Continuing hemodynamic success in this series was 80%, and was 87% with repeat stent placement in 1 patient.
Idiopathic intracranial hypertension (IIH) typically affects young, obese women. We examined 2 groups of atypical patients with IIH: those with a normal body mass index (BMI) and those at least 50 years of age.
A retrospective cohort study of 407 consecutive adult patients with IIH with known BMI from 3 centers was undertaken. Demographics, associated factors, visual acuity, and visual fields were collected at presentation and follow-up.
We identified 18 IIH patients (4%) with normal BMI and 19 (5%) aged 50 years or older at the time of diagnosis who were compared with the remainder of the cohort. Medication-induced IIH was more frequent in patients with IIH with normal BMI (28 vs 7%, p = 0.008). No patient with IIH with a normal BMI had severe visual loss in either eye (0 vs 17%, p = 0.09). Older patients with IIH had a lower BMI, but were still generally obese (33 vs 38, p = 0.04). Older patients were less likely to report headache as initial symptom (37 vs 76%, p < 0.001) and more likely to complain of visual changes (42 vs 21%, p = 0.03). Treatment of any type was less likely in older patients (significant for medications: 74 vs 91%, p = 0.004), and they were more likely to have persistent disc edema at last follow-up (median Frisén grade: 1 vs 0, p = 0.002), but had similar, if not better, visual outcomes compared with younger patients. A case-control study did not identify any new medication or risk factor associations.
Patients with normal body mass index and those 50 years or older make up a small proportion of patients with idiopathic intracranial hypertension (IIH), but appear to have better visual outcomes than more typical patients with IIH.
Brain water self diffusion was investigated by magnetic resonance scanning in 7 patients fulfilling conventional diagnostic criteria for pseudotumour cerebri. Quantitative diffusion measurements were obtained using single spin echo pulse sequences with pulsed magnetic field gradients of different magnitude. In all patients the diffusion images showed an increased diffusion in various brain regions when compared with the diffusion coefficients for corresponding regions in healthy subjects. In 3 pseudotumour patients the increased self diffusion was localized to the periventricular regions, while 4 patients had increased diffusion in the whole brain. The findings indicate the presence of increased brain water content both intra- and extracellularly suggesting that patients with pseudotumour have two defects of pathogenetical significance: intracellular water accumulation and increased resistance to cerebrospinal fluid (CSF) outflow leading to an interstitial oedema.
Arachnoid granulations and villi from 23 brains from subjects aged 9 to 84 years were examined post mortem by serial sections with the light microscope and as whole or fractured preparations in the scanning electron microscope. The object of the study was to investigate the pathways within the arachnoid granulations by which cerebrospinal fluid (CSF) drains from the subarachnoid space to the sinus endothelium. At the base of each granulation, a thin neck of arachnoid projects through an aperture in the dural lining of the sinus and expands to form a core of collagenous trabeculae and interwoven channels. An apical cap of arachnoid cells, about 150 microns thick, surmounts the collagenous core, and channels extend through the cap to reach subendothelial regions of the granulation. Channels within the granulation are lined by compacted collagen and may contain macrophages. Following recent subarachnoid hemorrhage, erythrocytes are found in the channels, suggesting that the channels are in continuity with the subarachnoid space and are CSF drainage pathways. The cap region of the granulation is only attached to the endothelium over an area 300 microns in diameter; the rest of the granulation core is separated from the endothelium by a subdural space and a fibrous dural cupola. Scanning electron microscopy reveals an intact endothelial surface to the granulations with small perforating venous channels present on the apex of some granulations. The differences between human arachnoid granulations and arachnoid villi in animals are discussed, together with preliminary observations regarding the transition of villi into granulations in man.
The volume of the lateral and third ventricles was measured by a non-invasive computerised axial tomographic method in 18 patients presenting with characteristic features of benign intracranial hypertension. Values obtained were significantly lower than in 18 controls matched for age and sex. The demonstration of smaller-than-normal ventricles in benign intracranial hypertension indicates that the syndrome is not primarily due to a disorder of cerebrospinal fluid absorption; rather, the increase in intracranial pressure may be caused by cerebral swelling, either due to oedema or engorgement.
We report three cases of masses within the cerebral dural venous sinuses shown with either MR or angiography. The dural venous sinuses of 10 patients without known venous disease were examined at autopsy. In two patients, three giant arachnoid granulations were identified. On the basis of the literature and our limited autopsy series, we suggest that these lesions identified at imaging are giant arachnoid granulations, normal variants of no known clinical significance.
To report the anatomic and radiologic development of the transverse, sigmoid, and occipital sinuses, the emissary veins, and the jugular bulb formation from the jugular sinus in humans before and after birth.
Roentgenograms of 33 injected brains showing the cranial venous system in human fetuses from 3 to 7 months of gestational age and cerebral angiograms of newborns and infants up to 6 years of age (23 clinical cases) were made and analyzed in detail. Special attention was focused on the inner diameters of the transverse and sigmoid sinuses and of the internal jugular veins, particularly at the sigmoid sinus-internal jugular vein junction.
Marked increase in venous flow from the rapidly growing cerebral hemispheres leads to ballooning of the transverse sinuses in the absence of an increase in the inner diameters of the sigmoid and jugular sinuses. The ballooning also results in formation of the occipital sinus, marginal sinus around the foramen magnum, and emissary veins. The formation of the jugular bulbs from the jugular sinuses begins after birth when a shift from a fetal to a postnatal type of circulation (or from a lying-down position to an erect posture) takes place.
The morphological changes of the posterior fossa dural sinuses, emissary veins, and jugular bulb are closely related to the development of the brain, shift to postnatal type of circulation, and postural hemodynamic changes.
To report the features of idiopathic intracranial hypertension in prepubertal children, with emphasis on presentation, treatment, and outcome.
We retrospectively reviewed the charts of all patients 11 years and younger diagnosed with idiopathic intracranial hypertension at two university-affiliated medical centers. Inclusion critera included papilledema, normal brain computed tomography or magnetic resonance imaging, cerebrospinal fluid pressure greater than 200 mm H2O, normal cerebrospinal fluid content, and a nonfocal neurologic examination except for sixth nerve palsy. Patients with concomitant systemic illness were excluded.
Of the 10 patients, four were girls and six were boys. Only one patient was obese. The most common presenting symptoms were stiff neck (four patients) and diplopia (four patients), and the most common presenting sign was strabismus (eight patients). Six of eight patients with strabismus had abducens nerve palsy (four bilateral), one patient had a sensory exotropia, and one had a comitant esotropia. Visual field abnormalities were present in 11 of 13 eyes (85%), and severe visual loss resulting in no light perception vision occurred in one eye of one patient. Nine patients were treated medically, four with a combination of prednisone or dexamethasone and acetazolamide and five with acetazolamide alone. One patient in this group also required a lumboperitoneal shunt. One patient was treated with lumbar puncture only. Resolution of papilledema occurred rapidly in all patients, with a mean of 4.7 +/- 2.6 months. Resolution of sixth nerve palsy also occurred rapidly in four of six patients in a mean of 1.6 +/- 1.2 months. One patient required strabismus surgery for persistent esotropia and one was lost to follow-up.
Idiopathic intracranial hypertension in prepubertal children is rare and is different than the disease in adults. In our series, there appeared to be no sex predilection, and obesity was uncommon. Children are likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment.
To determine the prevalence and nature of sinovenous obstruction in idiopathic intracranial hypertension (IIH) using auto-triggered elliptic-centric-ordered three-dimensional gadolinium-enhanced MR venography (ATECO MRV).
In a prospective controlled study, 29 patients with established IIH as well as 59 control patients underwent ATECO MRV. In a randomized blinded fashion, three readers evaluated the images. Using a novel scoring system, each reader graded the degree of stenosis seen in the transverse and sigmoid sinuses of each patient.
There was excellent agreement across the three readers for application of the grading system. Substantial bilateral sinovenous stenoses were seen in 27 of 29 patients with IIH and in only 4 of 59 control patients.
Using ATECO MRV and a novel grading system for quantifying sinovenous stenoses, the authors can identify IIH patients with sensitivity and specificity of 93%.
The cerebrospinal fluid (CSF) provides mechanical and chemical protection of the brain and spinal cord. This review focusses on the contribution of the choroid plexus epithelium to the water and salt homeostasis of the CSF, i.e. the secretory processes involved in CSF formation. The choroid plexus epithelium is situated in the ventricular system and is believed to be the major site of CSF production. Numerous studies have identified transport processes involved in this secretion, and recently, the underlying molecular background for some of the mechanisms have emerged. The nascent CSF consists mainly of NaCl and NaHCO(3), and the production rate is strictly coupled to the rate of Na(+) secretion. In contrast to other secreting epithelia, Na(+) is actively pumped across the luminal surface by the Na(+),K(+)-ATPase with possible contributions by other Na(+) transporters, e.g. the luminal Na(+),K(+),2Cl(-) cotransporter. The Cl(-) and HCO(3) (-) ions are likely transported by a luminal cAMP activated inward rectified anion conductance, although the responsible proteins have not been identified. Whereas Cl(-) most likely enters the cells through anion exchange, the functional as well as the molecular basis for the basolateral Na(+) entry are not yet well-defined. Water molecules follow across the epithelium mainly through the water channel, AQP1, driven by the created ionic gradient. In this article, the implications of the recent findings for the current model of CSF secretion are discussed. Finally, the clinical implications and the prospects of future advances in understanding CSF production are briefly outlined.
The glymphatic pathway
- H Benveniste
- Lee
- N D Volkow
Pseudotumor cerebri and glymphatic dysfunction
- Mls Bezerra
- A Ferreira
- R De Oliveira-Souza
- Bezerra MLS
Development of posterior fossa dural sinuses, emissary veins, and jugular bulb: morphological and radiologic study
- T Okudera
- Y P Huang
- T Ohta
- Okudera T