OBJECTIVE:The traditional view that hydrocephalus due to obstruction in the subarachnoid space (SAS) is caused by malabsorption of CSF does not account for many experimental and clinical aspects of the disorder. Flow MRI reveals that nearly all CSF motion is pulsatile, and that hydrocephalus is linked to significant redistribution of pulsatility within the CSF pathways. Pulsatility in the cranium is governed by the cerebral windkessel system that buffers the energy of arterial pulsations via CSF to ensure smooth capillary blood flow. This study proposes a new model of intracranial thermodynamics based on the theory that high impedance to pulsatile energy flow through the CSF pathways causes hydrocephalus. METHODS:The authors used a simple current-divider electrical circuit model of the cerebral windkessel system with input voltage derived from arterial blood pressure tracings from 12 normal dogs. SAS obstruction in the model was simulated using CSF flow values corresponding to published data from flow MRI studies of patients with hydrocephalus. RESULTS:Modeling of hydrocephalus due to subarachnoid obstruction shows windkessel impairment and redistribution of CSF pulsatility caused by high damping of pulsatility in the SAS. Modeling of ventricular dilation as an active physiological adaptation shows improved windkessel function. Modeling of shunting shows windkessel restoration. The model produces the salient features of hydrocephalus due to obstruction in the SAS without invoking CSF malabsorption. CONCLUSIONS:The authors propose that hydrocephalus due to SAS obstruction is impairment of the cerebral windkessel system due to high impedance to pulsatility in the subarachnoid CSF path that redistributes arterial pulsatile energy to the capillaries and jeopardizes capillary integrity. Windkessel theory introduces several new perspectives on hydrocephalus: 1) adaptive ventricular dilation is an active physiological response to windkessel impairment and lowers CSF path impedance to pulsations; 2) increased intracranial pressure (ICP) results from pressure energy accumulation due to windkessel dysfunction; 3) shunting is an accessory windkessel and reduces ICP by draining energy; 4) windkessel theory offers a new taxonomy of hydrocephalus, linking hydrocephalus due to SAS obstruction and hydrocephalus caused by aqueductal obstruction, normal pressure hydrocephalus, and low pressure hydrocephalus as related but distinct disorders of CSF path impedance; and 5) windkessel theory provides an explanation for hydrocephalus without invoking CSF malabsorption. Windkessel theory provides a new understanding of hydrocephalus and indicates new approaches to treatment.

Background: Hepatitis C virus (HCV) is the most common blood-borne virus, affecting tens of millions of people worldwide. Neurologic manifestations of chronic HCV are rare and may be overlooked during workup of central nervous system (CNS) infections. We report on a patient who was diagnosed with hepatitis C meningoencephalitis after a protracted treatment course for presumed methicillin-resistant Staphylococcus aureus (MRSA) ventriculitis. Case Description:This was a 34-year-old male with a history of intravenous drug use and ventriculoperitoneal shunt placement for hydrocephalus secondary to post-traumatic intracranial hemorrhage, who presented 1 week following shunt surgery with worsening dizziness, with initial assessment demonstrating shunt infection with positive MRSA on cerebrospinal fluid (CSF) cultures. Over his hospital course, the patient demonstrated worsening ventriculomegaly on imaging, with pleocytosis and hyperproteinosis on CSF analyses despite aggressive antibiotic treatment, ventricular irrigation, and negative bacterial and fungal cultures. His symptoms resolved within 1 week of antiviral therapy for HCV with sofosbuvir-velpatasvir. Conclusion:In patients with chronic HCV, viral reactivation may manifest as protracted ventriculitis in the setting of low-to-normal pressure ventriculomegaly. Providers should be cognizant of serologically covert viral etiologies for post-operative infections and consider preemptive antiviral treatment in patients with aseptic CSF profiles when refractory to empiric antibiotic regimens for more common CNS pathogens.

ObjectiveNormal pressure hydrocephalus (NPH) is characterized by ventriculomegaly without elevations in intracranial pressure (ICP). One way of viewing hydrocephalus is as a disorder of the cerebral windkessel. The cerebral windkessel is the system that dampens the arterial blood pressure (ABP) pulse in the cranium, transmitting this pulse from arteries to veins via the cerebrospinal fluid (CSF) path, bypassing the microvasculature to render capillary flow smooth. When the windkessel is physiologically tuned, windkessel effectiveness (W) is given by: W=IE/R, where I represents CSF path inertance (pulse magnitude), E is CSF path elastance, and R is resistance in the CSF path. In NPH, we posit that there is a combination of arteriosclerosis (blunting the CSF pulse in the SAS- lowering I), and age-related softening of brain tissue (decreasing the elastance of subarachnoid CSF pathways- lowering E).MethodsTo model the windkessel, we utilize a tank circuit with parallel inductance and capacitance to simulate the pulsatile flow of blood and CSF as alternating current (AC), and smooth flow as direct current (DC). We model NPH as a disorder of windkessel impairment by decreasing windkessel inertance (reflecting diminished CSF pulsatility in the SAS from arteriosclerosis) and decreasing intracranial elastance (reflecting age-related brain atrophy). We simulate ventriculomegaly and shunting by lowering the resistance of this circuit.ResultsIn simulating NPH using this circuit, we found significant elevations in the amplitude and power of AC in the CSF and capillary paths when inertance and elastance were decreased. Conversely, this pulse power decreased with decreased resistance in the CSF path from ventriculomegaly and shunting.ConclusionSimulations of NPH demonstrated increased amplitude and power of AC in the CSF and capillary paths due to windkessel impairment. We posit that this pulsatility is redistributed from the SAS to the ventricular CSF path, exerting pulsatile stress on the periventricular leg and bladder fibers, which may explain NPH symptomatology. Ventriculomegaly may represent an active adaptation to improve windkessel effectiveness by decreasing CSF path resistance to mitigate decreased CSF path inertance and parenchymal elastance. Shunting provides a low resistance, accessory windkessel to obviate adaptive ventriculomegaly. This has significant implications in understanding this paradoxical condition.

Long-standing overt ventriculomegaly in adults (LOVA) has been posited as a form of progressive hydrocephalus, with similar clinical and radiographic features to normal pressure hydrocephalus (NPH), but which should be understood as a distinct clinical entity. We conducted a narrative review analysing the literature into LOVA as a distinct form of hydrocephalus with its own clinical and radiographic characteristics and treatment modalities. LOVA is characterised by triventriculomegaly, an Evans' index of ≥0.4, presenting with progressive symptoms of elevated intracranial pressure after an initial arrest in childhood and head circumferences≥2 SD above the mean. Endoscopic third ventriculostomy is considered the first-line treatment. Shunting is equally effective but confers a higher complication risk profile. LOVA represents a progressive form of hydrocephalus with certain clinical and radiographic features which overlap with NPH, but is a distinct entity which should be on the neurologist's differential.

Normal pressure hydrocephalus (NPH) represents a unique form of hydrocephalus characterised by the paradox of ventriculomegaly without significant elevations in intracranial pressure, with the clinical triad of gait instability, cognitive impairment, and urinary incontinence. A myriad of neurobiological correlates have been implicated in its pathophysiology. We review the literature to provide an up-to-date, narrative review of the proposed mechanisms underlying the pathophysiology of NPH, proposing a holistic framework through which to understand the condition.We conducted a narrative review of the literature on NPH, assessing the various mechanisms underlying its pathophysiology and clinical presentation.NPH represents a unique form of hydrocephalus manifesting as a disorder of the cerebral vasculature, characterised by arteriosclerosis and reduced intracranial elastance. There are multiple mechanisms underlying its pathophysiology, which include windkessel impairment causing redistribution of intracranial pulsatility from the subarachnoid space to the ventricles, reductions in cerebral blood flow, impaired glymphatic clearance, reduced blood–brain barrier integrity and alterations in venous haemodynamics. Moreover, NPH shares similar clinical features and pathological mechanisms as other neurodegenerative conditions such as Alzheimer’s disease and vascular dementia. The severity of each respective mechanism of pathophysiology can lead a patient to develop one condition versus another.Analysing NPH as a disorder of the cerebral vasculature, glymphatics, and most of all, the distribution of intracranial pulsatility, provides a novel framework through which to understand and manage this condition, one which requires further investigation.

OBJECTIVE:Traditional models of intracranial dynamics fail to capture several important features of the intracranial pressure (ICP) pulse. Experiments show that, at a local amplitude minimum, the ICP pulse normally precedes the arterial blood pressure (ABP) pulse, and the cranium is a band-stop filter centered at the heart rate for the ICP pulse with respect to the ABP pulse, which is the cerebral windkessel mechanism. These observations are inconsistent with existing pressure-volume models.METHODS:To explore these issues, the authors modeled the ABP and ICP pulses by using a simple electrical tank circuit, and they compared the dynamics of the circuit to physiological data from dogs by using autoregressive with exogenous inputs (ARX) modeling.RESULTS:The authors' ARX analysis showed close agreement between the circuit and pulse suppression in the canine cranium, and they used the analogy between the circuit and the cranium to examine the dynamics that underlie this pulse suppression.CONCLUSIONS:This correspondence between physiological data and circuit dynamics suggests that the cerebral windkessel consists of the rhythmic motion of the brain parenchyma and CSF that continuously opposes systolic and diastolic blood flow. Such motion has been documented with flow-sensitive MRI. In thermodynamic terms, the direct current (DC) power of cerebral arterial perfusion drives smooth capillary flow and alternating current (AC) power shunts pulsatile energy through the CSF to the veins. This suggests that hydrocephalus and related disorders are disorders of CSF path impedance. Obstructive hydrocephalus is the consequence of high CSF path impedance due to high resistance. Normal pressure hydrocephalus (NPH) is the consequence of high CSF path impedance due to low inertance and high compliance. Low-pressure hydrocephalus is the consequence of high CSF path impedance due to high resistance and high compliance. Ventriculomegaly is an adaptive physiological response that increases CSF path volume and thereby reduces CSF path resistance and impedance. Pseudotumor cerebri is the consequence of high DC power with normal CSF path impedance. CSF diversion by shunting is an accessory windkessel-it drains energy (and thereby lowers ICP) and lowers CSF path resistance and impedance. Cushing's reflex is an accessory windkessel in extremis-it maintains DC power (arterial hypertension) and reduces AC power (bradycardia). The windkessel theory is a thermodynamic approach to the study of energy flow through the cranium, and it points to a new understanding of hydrocephalus and related disorders.

How consciousness arises in the brain has important implications for clinical decision-making. We summarize recent findings in consciousness studies to provide a toolkit for clinicians to assess deficits in consciousness and predict outcomes after brain injury. Commonly encountered disorders of consciousness are highlighted, followed by the clinical scales currently used to diagnose them. We review recent evidence describing the roles of the thalamocortical system and brainstem arousal nuclei in supporting awareness and arousal and discuss the utility of various neuroimaging studies in evaluating disorders of consciousness. We explore recent theoretical progress in mechanistic models of consciousness, focusing on 2 major models, the global neuronal workspace and integrated information theory, and review areas of controversy. Finally, we consider the potential implications of recent research for the day-to-day decision-making of clinical neurosurgeons and propose a simple "three-strikes" model to infer the integrity of the thalamocortical system, which can guide prognosticating return to consciousness.

OBJECTIVE Pseudotumor cerebri is a disorder of intracranial dynamics characterized by elevated intracranial pressure (ICP) and chronic cerebral venous hypertension without structural abnormalities. A perplexing feature of pseudotumor is the absence of the ventriculomegaly found in obstructive hydrocephalus, although both diseases are associated with increased resistance to cerebrospinal fluid (CSF) resorption. Traditionally, the pathophysiology of ventricular dilation and obstructive hydrocephalus has been attributed to the backup of CSF due to impaired absorption, and it is unclear why backup of CSF with resulting ventriculomegaly would not occur in pseudotumor. In this study, the authors used an electrical circuit model to simulate the cerebral windkessel effect and explain the presence of ventriculomegaly in obstructive hydrocephalus but not in pseudotumor cerebri. METHODS The cerebral windkessel is a band-stop filter that dampens the arterial blood pressure pulse in the cranium. The authors used a tank circuit with parallel inductance and capacitance to model the windkessel. The authors distinguished the smooth flow of blood and CSF and the pulsatile flow of blood and CSF by using direct current (DC) and alternating current (AC) sources, respectively. The authors measured the dampening notch from ABP to ICP as the band-stop filter of the windkessel. RESULTS In obstructive hydrocephalus, loss of CSF pathway volume impaired the flow of AC power in the cranium and caused windkessel impairment, to which ventriculomegaly is an adaptation. In pseudotumor, venous hypertension affected DC power flow in the capillaries but did not affect AC power or the windkessel, therefore obviating the need for adaptive ventriculomegaly. CONCLUSIONS In pseudotumor, the CSF spaces are unaffected and the windkessel remains effective. Therefore, ventricles remain normal in size. In hydrocephalus, the windkessel, which depends on the flow of AC power in patent CSF spaces, is impaired, and the ventricles dilate as an adaptive process to restore CSF pathway volume. The windkessel model explains both ventriculomegaly in obstructive hydrocephalus and the lack of ventriculomegaly in pseudotumor. This model provides a novel understanding of the pathophysiology of disorders of CSF dynamics and has significant implications in clinical management.

Abstract Background: Traditional models of intracranial dynamics fail to capture several important features of the cerebral windkessel. Experiments show that the cerebral windkessel is a band-stop filter tuned to the heart rate, which is not consistent with existing pressure-volume compartment models. Flow MRI studies in humans reveal expansion and relaxation of the cranial contents during the cardiac cycle that continuously opposes arterial expansion and relaxation, and we suggest this is the way the windkessel is implemented in the cranium. This systolic-diastolic brain motion is analogous to the loading and unloading of the capacitor plates in the model circuit.Methods: In this study, we use exogenous input autoregressive (ARX) modeling of a simple band-stop electrical circuit to model the cerebral windkessel of normal dogs. We compare the circuit waveforms to waveforms measured in dogs, and we examine the dynamics that underlie the cerebral windkessel.Results: Our ARX analysis shows close agreement between the circuit and the windkessel, which implies similar physical mechanisms of pulsation suppression. This correspondence between physiological data and circuit dynamics suggests that the cerebral windkessel is a frequency-sensitive band-stop filter for the passage of arterial power through the cranium. Another perspective from which to understand the windkessel is to consider the smooth offset and the pulsatile components of cerebral arterial flow as DC and AC power respectively. In the cranium, DC power of cerebral blood flow passes through the capillary bed to the veins and AC power is diverted through the CSF to the veins. This windkessel mechanism optimizes smooth capillary flow and minimizes potentially damaging capillary pulsatility.Conclusions: Our windkessel model provides substantial new insights into intracranial dynamics, cerebral blood flow and capillary circulation, and it provides a new framework for the study and treatment of several common disorders of intracranial dynamics such as cerebral edema, hydrocephalus, pseudotumor cerebri, and Cushing’s reflex.

The cerebral windkessel is the suppression of the arterial pulse in the cranium which renders capillary blood flow smooth. Arterial pressure and flow are normally synchronous, and (counterintuitively) the intracranial pressure (ICP) pulse slightly precedes the arterial blood pressure (ABP) pulse. Transfer function analysis of the ABP pulse to the ICP pulse shows a local minimum of amplitude response (a notch) at the heart rate, and abnormal intracranial dynamics attenuates the notch and shifts phase. I propose that these counterintuitive aspects of intracranial pulsatility may be understood by treating the cerebral windkessel as a designed system. On that basis, I here apply principles of reverse-engineering to model the ICP pulse first as a simple harmonic oscillator, then as a forced harmonic oscillator with one or two degrees of freedom. By including a model of the intra- and extra-capillary pathways, I show that ABP-ICP dynamics are characteristic of a dynamic pulsation absorber—a system of vibration suppression widely used in engineering. MRI flow imaging shows that this is accomplished by an arterial-cerebrospinal fluid (CSF)-venous pump. During systole, CSF links arterial expansion to venous compression. During diastole, CSF links venous expansion to arterial relaxation. Arterial pulsations pass through the CSF to the veins, and this transposition of the arterial pulse by venous compression and relaxation provides an elastic force that continuously opposes the radial motion of the capillary walls. This maintains the resonant dynamics necessary for efficient perfusion and the anti-resonant dynamics necessary for capillary protection. Maintenance of anti-resonant dynamics (crucial for preventing cerebral edema and capillary damage) requires a system of autoregulation of intracranial pulsatility, which the cerebral windkessel provides.

Background: We investigated a novel surgical approach to decompressive craniectomy (DC), the bifrontal biparietal, or “cruciate,” craniectomy, in severe pediatric traumatic brain injury (TBI). Cruciate DC was designed with a fundamentally different approach to intracranial pressure (ICP) control compared to traditional DC. Cruciate DC involves craniectomies in all 4 skull quadrants. The sagittal and coronal bone struts are disarticulated at the skull to allow the decompression of the sagittal sinus and bridging veins in addition to permitting cerebral expansion, thereby maintaining cranial compliance. Objective: To characterize ICP control with cruciate DC in pediatric TBI. Methods: We performed a retrospective review of TBI patients who underwent cruciate DC. We investigated mortality and preoperative and postoperative ICP. Group 1 underwent medical therapy prior to DC and Group 2 required immediate DC. Results: Fifteen of 18 patients survived. In Group 1, mean preoperative ICP was 18.5 mm Hg and mean postoperative ICP was 11.5 mm Hg. In Group 2, mean preoperative ICP was 27.3 mm Hg and mean postoperative ICP was 15.0 mm Hg. Conclusion: Cruciate DC was associated with lowering ICP. We observed acute drops in ICP and long-term ICP control. The floating bone struts of the cruciate DC permits the decompression of the sagittal sinus and bridging veins, with maximal relief of cerebral edema.

BACKGROUND CONTEXT: Two of the most common disease processes associated with hydrocephalus in children are spina bifida and intraventricular hemorrhage of prematurity, both of which are known to be also associated with spinal deformity in later childhood. The occurrence of shunt malfunction after mechanical injury or stress to the hardware has been well documented. Newer techniques in the treatment of neuromuscular scoliosis, including anterior release with segmental fixation, have resulted in more powerful corrections of these large spinal deformities. A new potential cause of shunt malfunction is the aggressive correction of scoliosis. PURPOSE: To report patients with neuromuscular curves averaging 100 degrees who were subsequently recognized to have perioperative shunt malfunction. STUDY DESIGN: Three case studies from a university hospital setting were included. PATIENT SAMPLE: All three children were young adolescents and had-long term shunts. Two of the children had spina bifida and a third had cerebral palsy. All children underwent anterior release of their scoliosis with posterior segmental instrumentation, with unit rods and sublaminar wires. All had significant correction of their scoliosis. OUTCOME MEASURES: Malfunctioning of the ventriculoperitoneal shunts were recorded. METHODS: Chart reviews of three cases were analyzed. RESULTS: Two children had shunt malfunctions within a month of their surgery, and one child had intraoperative recognition and externalization of the shunt. CONCLUSIONS: Older children undergoing repair of neuromuscular scoliosis are often preadolescents or adolescents who have the same indwelling shunt systems originally implanted in early infancy. The shunt may be brittle and calcified, and the peritoneal catheter may be short. The correction of scoliosis often results in an almost instantaneous growth of a few inches. Because of the potential difficulty in recognizing shunt malfunction in the perioperative period, consideration should be given for elective revision of the peritoneal catheter in children at risk. (C) 2014 Elsevier Inc. All rights reserved.

OBJECT:The intracranial pulse pressure is often increased when neuropathology is present, particularly in cases of increased intracranial pressure (ICP) such as occurs in hydrocephalus. This pulse pressure is assumed to originate from arterial blood pressure oscillations entering the cranium; the fact that there is a coupling between the arterial blood pressure and the ICP is undisputed. In this study, the nature of this coupling and how it changes under conditions of increased ICP are investigated.METHODS:In 12 normal dogs, intracarotid and parenchymal pulse pressure were measured and their coupling was characterized using amplitude and phase transfer function analysis. Mean intracranial ICP was manipulated via infusions of isotonic saline into the spinal subarachnoid space, and changes in transfer function were monitored.RESULTS:Under normal conditions, the ICP wave led the arterial wave, and there was a minimum in the pulse pressure amplitude near the frequency of the heart rate. Under conditions of decreased intracranial compliance, the ICP wave began to lag behind the arterial wave and increased significantly in amplitude. Most interestingly, in many animals the pulse pressure exhibited a minimum in amplitude at a mean pressure that coincided with the transition from a leading to lagging ICP wave.CONCLUSIONS:This transfer function behavior is characteristic of a resonant notch system. This may represent a component of the intracranial Windkessel mechanism, which protects the microvasculature from arterial pulsatility. The impairment of this resonant notch system may play a role in the altered pulse pressure in conditions such as hydrocephalus and traumatic brain swelling. New models of intracranial dynamics are needed for understanding the frequency-sensitive behavior elucidated in these studies and could open a path for development of new therapies that are geared toward addressing the pulsation dysfunction in pathological conditions, such as hydrocephalus and traumatic brain injury, affecting ICP and flow dynamics.

OBJECT:The relationship between the waveform of intracranial pressure (ICP) and arterial blood pressure can be quantitatively characterized using a newly developed technique in systems analysis, the time-varying transfer function. This technique considers the arterial blood pressure as an input signal composed of multiple frequencies represented in the output ICP according to the transfer function imposed by the intracranial system on the input signal. The transfer function can change with time and with physiological manipulations. The authors examined data obtained from canine experiments involving manipulations of ICP.METHODS:The authors analyzed 11 experiments from 3 normal mongrel dogs under conditions of normal ICP and with changes in ICP made by bolus injection, infusion, or withdrawal of cerebrospinal fluid by using time-varying transfer function.RESULTS:During normal ICP periods, the gain of the transfer function displayed a deep notch (> or = 1 log unit) centered at or near the cardiac frequency. In systems terms, the intracranial compartment under normal conditions appears to act as a notch filter attenuating the cardiac frequency input relative to other frequencies. Epochs of ICP elevation showed suppression of the notch, and the notch was restored when ICP returned to normal.CONCLUSIONS:The intracranial system in these animals could be considered to include a pulsation absorber for which the target frequency appears to be close to the cardiac frequency. One possible source for such an absorber mechanism might be the free movement of cerebrospinal fluid, implying that impairment of this motion may have important clinical implications in various neurological conditions such as hydrocephalus.

Communicating hydrocephalus (CH) occurs frequently, but clinically-relevant animal models amenable to diagnostic imaging and cerebrospinal fluid shunting are not available. In order to develop and characterize models of subarachnoid space (SAS) obstruction at the basal cisterns (BC) or cerebral convexities (CX), 25% kaolin was injected in adult female Sprague-Dawley rats following halothane anesthesia; intact- or saline-injected animals served as controls. For BC animals (n=28 hydrocephalics, n=20 controls), an anterior approach to the C1-clivus interval was employed and 30 microl of kaolin or saline was injected. For CX injections (n=13 hydrocephalics, n=3 controls), 50-60 microl of kaolin was injected bilaterally after separating the partitions in the SAS. In BC-injected rats, kaolin was observed grossly in the basal cisterns but not in the cisterna magna or at the foramina of Luschka, indicating that communicating (or extra-ventricular)--not obstructive--hydrocephalus had been induced. Following ketamine/xylazine anesthesia, magnetic resonance imaging (MRI) of gadolinium injected into the lateral ventricle also demonstrated CSF flow from the foramina of Luschka. MRI also revealed that ventriculomegaly progressed steadily in BC animals and by 2 weeks post-kaolin the mean Evan's ratio (frontal horn) increased significantly (mean 0.45 compared to 0.31 in intact- and 0.34 in saline-injected controls; p<0.001 for each). CX animals exhibited kaolin deposits covering approximately 80% of the cerebral hemispheres and developed noticeable ventriculomegaly (mean Evan's ratio 0.40), which was significant relative to intact animals (p=0.011) but not saline-injected controls. Surprisingly, ventriculomegaly following CX injections was less severe and much more protracted, requiring 3-4 months to develop compared to ventriculomegaly produced by BC obstruction. No hydrocephalic animals demonstrated obvious neurological deficits, but BC-injected animals that subsequently developed more severe ventriculomegaly exhibited nasal discharges and "coughing" for several days following kaolin injection. The new BC model is relevant because the clinical presentation of CH in children is often associated with obstruction at this site, while the CX model may be more representative of late adult onset normal pressure hydrocephalus.

Background In communicating hydrocephalus (CH), where either there is no obvious physical blockage within the subarachnoid space, or the obstruction can be variable in location, explanations for the symptoms and clear-cut effective treatments have been elusive. A few investigators have begun to stress the importance of pulsatile vascular and CSF dynamics. While it is known that pulsatile flow through the cerebral aqueduct is often significantly elevated in hydrocephalus, a clear link between abnormal pulsations and ventriculomegaly has been yet to be established. The purpose of this study was to characterize the temporal changes in intracranial pulsatility in a novel model of CH.