Naokazu Hayashi

Research into the Physiology of Cerebrospinal Fluid Reaches a New Horizon: Intimate Exchange between Cerebrospinal Fluid and Interstitial Fluid May Contribute to Maintenance of Homeostasis in the Central Nervous System

Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016.

The Striate Artery, Hematoma, and Spot Sign on Coronal Images of Computed Tomography Angiography in Putaminal Intracerebral Hemorrhage

Background and Purpose— A spot sign is a bright spot on computed tomography angiography source images, which is predictive of hematoma growth in spontaneous intracerebral hemorrhage, although the cause of the spot sign is unclear. Our aim was to investigate the spot sign seen on computed tomography angiography and a striate artery, which is a presumed site of intracerebral hemorrhage bleeding origin in the putamen. Methods— In consecutive cases of spontaneous intracerebral hemorrhage in the putamen, spot signs and striate arteries were evaluated. Coronal reformat images of computed tomography angiography were created to visualize the striate arteries. Acute deterioration, defined as hematoma enlargement, emergency hematoma removal, or death within the day of admission, was reviewed. Results— Of the 141 patients undergoing computed tomography angiography, 15 of the 30 patients (50%) who had spot signs showed an intrahematoma striate artery (termed spot and tail sign), which was a linear density extending from the middle cerebral artery toward the spot sign. Acute deterioration occurred more frequently in patients who had a spot and tail sign compared with patients who had spot signs without intrahematoma striate arteries (P<0.05). Multivariate analysis revealed that hematoma volume, spot signs, and intrahematoma striate arteries were independent predictors of acute deterioration (P<0.05). Conclusions— The presence of a spot and tail sign, assumed to indicate active bleeding from the striate artery, could be a more sensitive predictor of acute deterioration than the presence of a simple spot sign.

Quantitative Analysis of Cerebrospinal Fluid Pressure Gradients in Healthy Volunteers and Patients with Normal Pressure Hydrocephalus

Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image.

Magnetic Resonance Imaging Technique for Visualization of Irregular Cerebrospinal Fluid Motion in the Ventricular System and Subarachnoid Space

BACKGROUND Many studies have shown that cerebrospinal fluid (CSF) behaves irregularly, rather than with laminar flow, in the various CSF spaces. We adapted a modified previously known magnetic resonance imaging technique to visualize irregular CSF motion. Subsequently, we assessed the usefulness and clinical significance of the present method. MATERIALS AND METHODS Normal CSF motion in 10 healthy volunteers was visualized with the dynamic improved, motion-sensitized, driven-equilibrium steady-state free precession technique. Subsequently, CSF motion visualization with a modified sequence was applied to 3 patients. RESULTS In healthy volunteers, we achieved visualization of the irregularity of CSF flow in the ventricles and spinal canal, whereas CSF motion was diminished in the peripheral part of the intracranial subarachnoid space. In one case, we confirmed the patency of the patients third ventriculostomy fenestration site. In the other, we verified the usefulness of the proposed sequence for determining the communication between the ventricle or subarachnoid space and the cyst. CONCLUSIONS Using the present sequence, we obtained images that accentuated CSF motion, which is largely composed of irregular motion. This method does not require pulse triggering or complex post-processing of images and allows visualization of CSF motion in a short period of time in selected whole imaging planes. It can therefore be applied clinically to diagnose various diseases that cause abnormalities in the CSF space.

Endoscopic Microvascular Decompression with Transposition for Trigeminal Neuralgia and Hemifacial Spasm: Technical Note.

Background Endoscopic microvascular decompression (MVD) offers reliable identification of neurovascular conflicts under superb illumination, and it provides minimally invasive surgery for trigeminal neuralgia and hemifacial spasm. Transposition techniques have been reported as a decompression method to prevent adhesion and granuloma formation around decompression sites, providing better surgical outcomes. The feasibility and effects of transposition under endoscopic MVD were evaluated. Material and Methods Fully endoscopic MVD was performed using 4‐mm 0‐ and 30‐degree endoscopes. The endoscope was fixed with a pneumatic holding system, and a bimanual technique using single‐shaft instruments was performed. Transposition was performed with Teflon felt string and fibrin glue. Surgical results were evaluated using the scoring system proposed by Kondo et al. Results The endoscope was introduced via a retrosigmoid keyhole. The 0‐degree endoscope was advanced through the lateral aspect of the cerebellar tentorial surface to the trigeminal nerve in cases of trigeminal neuralgia and through the petrosal surface of the cerebellum to the facial nerve in cases of hemifacial spasm. Neurovascular conflicts and perforators from the offending artery were clearly demonstrated under the 30‐degree endoscopic view, and transposition of the offending artery was safely performed with preservation of perforators. Clinical symptoms improved without permanent complications. Conclusion Endoscopic MVD with the transposition technique is feasible. Superb endoscopic views demonstrate perforators arising from the offending artery behind the corner, allowing damage to perforators to be avoided during the transposition technique. Endoscopic MVD using the transposition technique is expected to offer excellent surgical results.

Endoscopic Middle Cranial Fossa Reconstruction with a Subtemporal Keyhole

BACKGROUND Skull base reconstruction is an essential technique for repairing cerebrospinal fluid (CSF) leakage. A reliable method for middle cranial fossa (MCF) reconstruction with minimal invasiveness has not been reported. An initial case of endoscopic MCF reconstruction with a subtemporal keyhole is described. CASE DESCRIPTION A 57-year-old man developed severe meningitis and was diagnosed with spontaneous CSF leakage from bone defects on the tegmen tympani. Endoscopic MCF reconstruction with a subtemporal keyhole was carried out. Three skin incisions, including 1 subtemporal incision for a subtemporal keyhole and 2 temporal line incisions on the superior temporal line, were made, and a 0-degree endoscope was introduced into the subcutaneous space. The deep temporal fascia (DTF) was bluntly dissected and separated from the superficial temporal fascia and the temporal muscle, and the DTF was incised to shape a pedicled flap under endoscopic view. Blood supply to the pedicled DTF flap was confirmed with indocyanine green angiography. A subtemporal keyhole was then made, and a 30-degree endoscope was used to explore the extradural space of the MCF floor, visualizing the bone defects on the tegmen tympani. The vascularized DTF flap passed easily through the subtemporal keyhole and adequately overlaid the bone defects. The patients postoperative course was uneventful, and the CSF leakage disappeared without mastication problems. CONCLUSIONS This purely endoscopic technique using a vascularized DTF flap provided reliable MCF reconstruction through a subtemporal keyhole. This technique is also expected to be applicable for MCF reconstruction after subtemporal keyhole surgery for skull base tumors.

Cardiac-driven Pulsatile Motion of Intracranial Cerebrospinal Fluid Visualized Based on a Correlation Mapping Technique

Purpose: A correlation mapping technique delineating delay time and maximum correlation for characterizing pulsatile cerebrospinal fluid (CSF) propagation was proposed. After proofing its technical concept, this technique was applied to healthy volunteers and idiopathic normal pressure hydrocephalus (iNPH) patients. Methods: A time-resolved three dimensional-phase contrast (3D-PC) sampled the cardiac-driven CSF velocity at 32 temporal points per cardiac period at each spatial location using retrospective cardiac gating. The proposed technique visualized distributions of propagation delay and correlation coefficient of the PC-based CSF velocity waveform with reference to a waveform at a particular point in the CSF space. The delay time was obtained as the amount of time-shift, giving the maximum correlation for the velocity waveform at an arbitrary location with that at the reference location. The validity and accuracy of the technique were confirmed in a flow phantom equipped with a cardiovascular pump. The technique was then applied to evaluate the intracranial CSF motions in young, healthy (N = 13), and elderly, healthy (N = 13) volunteers and iNPH patients (N = 13). Results: The phantom study demonstrated that root mean square error of the delay time was 2.27%, which was less than the temporal resolution of PC measurement used in this study (3.13% of a cardiac cycle). The human studies showed a significant difference (P < 0.01) in the mean correlation coefficient between the young, healthy group and the other two groups. A significant difference (P < 0.05) was also recognized in standard deviation of the correlation coefficients in intracranial CSF space among all groups. The result suggests that the CSF space compliance of iNPH patients was lower than that of healthy volunteers. Conclusion: The correlation mapping technique allowed us to visualize pulsatile CSF velocity wave propagations as still images. The technique may help to classify diseases related to CSF dynamics, such as iNPH.

Hemiparesis without Responsible Hematomas in Patients with Subarachnoid Hemorrhage Undergoing Early Aneurysmal Repair

OBJECTIVE The presence of hemiparesis on arrival in patients with subarachnoid hemorrhage (SAH) is presumed to affect prognosis; intracranial hematomas with mass effect responsible for hemiparesis are frequently observed in these patients. The aim of this study was to clarify characteristics and outcomes of patients who presented with hemiparesis on arrival with no responsible hematomas (hemiparesis without hematoma) having mass effect demonstrated on computed tomography. METHODS Consecutive patients with SAH treated with surgery for ruptured cerebral aneurysms within 5 days of onset between 2003 and 2015 were retrospectively reviewed. RESULTS Hemiparesis without hematoma was present in 25 of 858 surgically treated patients (2.9%). Internal carotid artery aneurysms were significantly more common in patients with hemiparesis without hematoma than in the other patients (P < 0.05). In 19 of 21 surviving patients (90.5%) with hemiparesis without hematoma on arrival, the hemiparesis improved at discharge. Favorable outcomes were achieved in 16 of 25 patients with hemiparesis without hematoma (64%) and in 13 of 59 patients with hemiparesis with hematomas (22.0%); this difference was significant (P < 0.05). CONCLUSIONS Hemiparesis can be expected to improve in patients with SAH with hemiparesis without hematoma, and such patients appear to have a better prognosis than patients with SAH with hemiparesis and responsible hematomas. A possible major mechanism of hemiparesis without hematoma based on the characteristics identified is a combination of transient ipsilateral hemispheric functional failure caused by the impact of aneurysmal rupture and transient ischemia of the perforators originating from the internal carotid artery.

The Choroid Plexus of the Lateral Ventricle As the Origin of CSF Pulsation Is Questionable

The advent of magnetic resonance imaging (MRI) enables noninvasive measurement of cerebrospinal fluid (CSF) motion, and new information about CSF motion has now been acquired. The driving force of the CSF has long been thought to be choroid plexus (CP) pulsation, but to investigate whether this phenomenon actually occurs, CSF motion was observed in the ventricular system and subarachnoid space using MRI. Eleven healthy volunteers, ranging in age from 23 to 58 years, participated in this study. The MRI sequences used were four-dimensional phase-contrast (4D-PC) and time-spatial labeling inversion pulse (t-SLIP). The 4D-PC images included sagittal images in the cranial midline, coronal images focusing on the foramen of Monro (FOM), and oblique coronal images of the trigone to quantify CSF velocity and acceleration. These values were compared and analyzed as non-parametric data using the Kolmogorov-Smirnov test and the Mann-Whitney U test. 4D-PC showed that the median CSF velocity was significantly lower in the posterior part of the lateral ventricle than in other regions. The quantitative analysis of velocity and acceleration showed that they were decreased around the CP in the trigone. Image analysis of both velocity mapping and t-SLIP showed suppressed CSF motion around the CP in the trigone. These findings cast doubt on CP pulsation being the driving force for CSF motion.