Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment‐resistant late‐life depression: A potential biomarker of microvascular angiopathy

Naish, Josephine H.; Baldwin, Robert C.; Patankar, Tufail; Jeffries, Suzanne; Burns, Alistair; Taylor, Chris; Waterton, John C.; Jackson, Alan

doi:10.1002/mrm.20999

Cited by 18 publications

(19 citation statements)

References 39 publications

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“…This hydraulic system, which behaves like a second-order low-pass filter, is a finely tuned mechanism that relies on the correct timing of the individual arterial, venous, and CSF pulses (28). Abnormalities in the cerebral arterial and venous pulses can greatly influence the performance of the hydraulic regulatory mechanism, (28,29) resulting in increased CSF pulsatility-something that has previously been implicated in a number of pathologies, including microvascular angiopathy, (30) communicating hydrocephalus (31), and leukoaraiosis (32).…”

Section: Discussionmentioning

confidence: 99%

Cine cerebrospinal fluid imaging in multiple sclerosis

Magnano

Schirda

Weinstock‐Guttman

et al. 2012

Magnetic Resonance Imaging

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Purpose: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. Materials and Methods:In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age-and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes.Results: Significantly decreased CSF net flow was detected in MS patients compared to HC (À3.7 vs. À7.1 mL/beat, P ¼ 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P ¼ 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05).Conclusion: CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.

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Section: Discussionmentioning

confidence: 99%

Cine cerebrospinal fluid imaging in multiple sclerosis

Magnano

Schirda

Weinstock‐Guttman

et al. 2012

Magnetic Resonance Imaging

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“…Still, mounting evidence indicates that the BCSFB and BBB are complexly interactive physiologically and in pathologic states. By integrating data for CP, ependyma, arachnoid and BBB vasculopathy, insight will be gained on how CSF-ISF dynamics impacts brain integrity [287]. …”

Section: Developing Translationally Effective Models For Restoringmentioning

confidence: 99%

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

Johanson

Duncan

Klinge

et al. 2008

Fluids Barriers CNS

713

704

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This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces.Outline1 Overview2 CSF formation2.1 Transcription factors2.2 Ion transporters2.3 Enzymes that modulate transport2.4 Aquaporins or water channels2.5 Receptors for neuropeptides3 CSF pressure3.1 Servomechanism regulatory hypothesis3.2 Ontogeny of CSF pressure generation3.3 Congenital hydrocephalus and periventricular regions3.4 Brain response to elevated CSF pressure3.5 Advances in measuring CSF waveforms4 CSF flow4.1 CSF flow and brain metabolism4.2 Flow effects on fetal germinal matrix4.3 Decreasing CSF flow in aging CNS4.4 Refinement of non-invasive flow measurements5 CSF volume5.1 Hemodynamic factors5.2 Hydrodynamic factors5.3 Neuroendocrine factors6 CS...

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“…We hypothesized that the reduction in arteriolar compliance would lead to a reduction in the delay between the arterial and CSF systolic pulses and a narrowing of the systolic pulse wave in the cerebral aqueduct, reflecting a reduction in the dampening mechanism within the arterial tree. These hypotheses were supported by the study, 55 suggesting that disturbances of cerebral hydrodynamics can be used to provide a generic biomarker of microvascular disease in patients with MVA. Recent findings in our laboratory (unpublished data) support this suggestion with the demonstration of abnormal CSF aqueductal flow patterns in elderly normal volunteers with high levels of vascular risk factors, compared with control subjects with low risk.…”

Section: Microvascular Angiopathymentioning

confidence: 54%

“…13 There are problems with all of these hypothesized mechanisms, in that the varying sets of phenomenological observations regarding arterial, venous, and CSF flow patterns are commonly open to differing interpretations. As described above in previous work from our laboratory, Naish et al 55 examined the transmission of the systolic pulse wave into the cerebral capillaries in elderly patients with treatment-resistant depression. The study demonstrated an increased aqueductal flow volume implying increased cerebral pulsatility with a decrease in the latency between arteriolar and aqueductal systole.…”

Section: Recent Advances In Csf Modelingmentioning

confidence: 96%

“…In a recent study 55 we hypothesized that the reduction in microvascular compliance caused by MVA would result in detectable changes in CSF flow in the cerebral aqueduct, due to increased passage of the systolic pulse wave into the cerebral capillary bed. We tested this hypothesis in a group of patients with late onset depression, in which there is considerable evidence that treatment resistance and other features of intractable disease result from vascular insult due to MVA.…”

Section: Microvascular Angiopathymentioning

confidence: 99%

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Changing Concepts of Cerebrospinal Fluid Hydrodynamics: Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease

Stivaros

Jackson

2007

Neurotherapeutics

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Summary: Phase-contrast magnetic resonance imaging (PC-MRI) or flow-sensitive MRI can be used to noninvasively measure intracranial vascular and CSF flow. Monro-Kellie homeostasis is the complex compensatory mechanism for the increase in intracranial blood volume during systole. Through PC-MRI techniques, our understanding of Monro-Kellie homeostasis and the associated intracranial hydrodynamics has greatly improved. Failure of this homeostatic mechanism has been implicated in a wide range of cerebral disorders, including vascular and Alzheimer's dementia, late-onset depression, benign and secondary intracranial hypertension, communicating and normal pressure hydrocephalus, and age-related white matter changes. The most common mode of homeostatic failure is due to vascular disease with decreased cerebral arterial compliance. This has wide-reaching implications in the investigation of patients with cerebral vascular disease. Here we discuss the role of PC-MRI in the study of cerebral hydrodynamics and the current understanding of Monro-Kellie homeostasis in both healthy and disease states. Quantitative assessment of the changes in this homeostatic mechanism using PC-MRI has important implications in the development of biomarkers of vascular involvement in disease with application in diagnosis, treatment planning, phenotype identification, and outcome assessment in clinical trials.

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Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment‐resistant late‐life depression: A potential biomarker of microvascular angiopathy

Cited by 18 publications

References 39 publications

Cine cerebrospinal fluid imaging in multiple sclerosis

Cine cerebrospinal fluid imaging in multiple sclerosis

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

Changing Concepts of Cerebrospinal Fluid Hydrodynamics: Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease

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