Deformable 3D-2D registration for high-precision guidance and verification of neuroelectrode placement.

Purpose.Accurate neuroelectrode placement is essential to effective monitoring or stimulation of neurosurgery targets. This work presents and evaluates a method that combines deep learning and model-based deformable 3D-2D registration to guide and verify neuroelectrode placement using intraoperative imaging.Methods.The registration method consists of three stages: (1) detection of neuroelectrodes in a pair of fluoroscopy images using a deep learning approach; (2) determination of correspondence and initial 3D localization among neuroelectrode detections in the two projection images; and (3) deformable 3D-2D registration of neuroelectrodes according to a physical device model. The method was evaluated in phantom, cadaver, and clinical studies in terms of (a) the accuracy of neuroelectrode registration and (b) the quality of metal artifact reduction (MAR) in cone-beam CT (CBCT) in which the deformably registered neuroelectrode models are taken as input to the MAR.Results.The combined deep learning and model-based deformable 3D-2D registration approach achieved 0.2 ± 0.1 mm accuracy in cadaver studies and 0.6 ± 0.3 mm accuracy in clinical studies. The detection network and 3D correspondence provided initialization of 3D-2D registration within 2 mm, which facilitated end-to-end registration runtime within 10 s. Metal artifacts, quantified as the standard deviation in voxel values in tissue adjacent to neuroelectrodes, were reduced by 72% in phantom studies and by 60% in first clinical studies.Conclusions.The method combines the speed and generalizability of deep learning (for initialization) with the precision and reliability of physical model-based registration to achieve accurate deformable 3D-2D registration and MAR in functional neurosurgery. Accurate 3D-2D guidance from fluoroscopy could overcome limitations associated with deformation in conventional navigation, and improved MAR could improve CBCT verification of neuroelectrode placement.

High-Resolution MRI for Evaluation of Ventriculostomy Tubes: Assessment of Positioning and Proximal Patency.

BACKGROUND AND PURPOSE: Imaging evaluation of ventriculostomy tubes, despite the frequency of malfunction, has remained inadequate due to the absence of a systematic way of assessing the catheter itself. In this retrospective review, we assessed the utility of high-resolution 3D MR imaging techniques, including CISS and volumetric interpolated breath-hold examination sequences, in the evaluation of ventriculostomy catheters. MATERIALS AND METHODS: We performed a retrospective review of 23 clinical MR imaging cases of shunted hydrocephalus spanning a 3-year period, all depicting ventriculostomy catheters. The MR imaging examinations included isotropic CISS and volumetric interpolated breath-hold examination sequences performed with and without contrast. These were independently evaluated by 2 neuroradiologists with respect to the catheter course, side hole position, relationship of the side holes to the ventricles, patency, and the presence or absence of intraluminal debris. RESULTS: The catheter tip was best seen on isotropic CISS sequences reformatted in an oblique plane, and side holes were visualized as CSF signal defects along the catheter wall in 10/23 (43%) cases. The relationship of the catheter side holes to the ventricles was seen in 47% of cases and was best visualized on the coronal CISS sequences. Catheter patency was confirmed in 12/23 (52%) cases, while the other 48% were notable for T2 hypointense filling defects compatible with luminal obstruction. Enhancement of some of these filling defects on imaging is suggestive of choroid plexus ingrowth rather than debris. CONCLUSIONS: High-resolution 3D MR imaging using isotropic CISS sequences allows systematic evaluation of catheter positioning, patency, and potential etiologic differentiation of filling defects when shunt dysfunction is suspected.

Chiari 1000 Registry Project: assessment of surgical outcome on self-focused attention, pain, and delayed recall.

BACKGROUND: Prior research has typically found a negative relationship between chronic pain and memory, and we examined whether cognitive control processes (e.g. reflection and rumination) moderated this relationship in individuals with Chiari malformation Type I (CM). CM is a neurological condition in which the cerebellar tonsils descend into the medullary and upper cervical spine regions potentially resulting in severe headaches and neck pain. METHODS: CM patients who had (n = 341) and had not (n = 297) undergone decompression surgery completed the McGill Pain Questionnaire-Short Form-Revised (SF-MPQ-2), the Rey Auditory Verbal Learning Test (RAVLT), and the Rumination-Reflection Questionnaire (RRQ). Immediate recall scores were compared to those of 102 healthy controls, and delayed recall performance was compared across other variables within the CM group. RESULTS: CM patients performed more poorly on immediate recall than did controls. Within CM patients, we observed main effects for reflection and age, and a pain x reflection x surgical status (surgery v. no surgery) interaction in which non-decompressed individuals with low levels of pain and high levels of reflection showed superior delayed recall relative to non-decompressed individuals with higher pain and all decompressed individuals. CONCLUSIONS: CM patients show an immediate recall deficit relative to controls, regardless of surgical status. High levels of reflection were associated with better delayed recall performance in non-decompressed CM patients with lower pain levels. High levels of chronic pain may overwhelm increased focused attention abilities, but higher levels of reflection partially overcome the distracting effects of pain and this may represent a type of resilience.

Investigation on the Effect of Drill Geometry and Pilot Holes on Thrust Force and Burr Height When Drilling an Aluminium/PE Sandwich Material.

Composite materials are widely employed in the naval, aerospace and transportation industries owing to the combination of being lightweight and having a high modulus of elasticity, strength and stiffness. Drilling is an operation generally used in composite materials to assemble the final product. Damages such as the burr at the drill entrance and exit, geometric deviations and delamination are typically found in composites subjected to drilling. Drills with special geometries and pilot holes are alternatives used to improve hole quality as well as to increase tool life. The present study is focused on the drilling of a sandwich composite material (two external aluminum plates bound to a polyethylene core). In order to minimize thrust force and burr height, the influence of drill geometry, the pilot hole and the cutting parameters was assessed. Thrust force and burr height values were collected and used to perform an analysis of variance. The results indicated that the tool and the cutting speed were the parameters with more weight on the thrust force and for burr height they were the tool and the interaction between tool and feed. The results indicated that drilling with a pilot hole of Ø4 mm exhibited the best performance with regard to thrust force but facilitated plastic deformation, thus leading to the elevation of burr height, while the lowest burr height was obtained using the Brad and Spur drill geometry.

Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (P

Adult-onset hydrocephalus.

Adult-onset hydrocephalus can be acquired from other pathologies, congenital with a late onset, or idiopathic. Subarachnoid hemorrhage, normal-pressure hydrocephalus, tumors, and aqueductal stenosis are the most frequent causes, and clinical presentation may be acute or chronic. The pathophysiology of the more chronic form involves hypoxia and blood vessel changes. The treatment of adult hydrocephalus is dependent on its setting and may involve ventroposterior or ventroanterior shunting or endoscopic procedures.

Clinical features of late-onset idiopathic aqueductal stenosis.

BACKGROUND: Although late-onset idiopathic aqueductal stenosis (LIAS) is considered a good indication for endoscopic third ventriculostomy (ETV), the characteristics of this clinical entity have seldom been reported in the magnetic resonance (MR) imaging era. The authors reviewed their patients with LIAS who were treated by ETV to confirm its clinical features and response to treatment. METHODS: The study group was composed of 31 patients diagnosed with LIAS who were previously untreated. Both anatomic and cine phase-contrast MR studies were used to detect the obstruction of the aqueduct canal. The preoperative symptoms were statistically analyzed in relation to the age of the patients and the degree of preoperative ventriculomegaly. RESULTS: The overall success rate of ETV was 83.9% with mean follow-up duration of 26.2 months. Only two patients had acute onset (within one month) without any predisposing chronic symptoms. The patients with chronic symptoms (longer than 6 months [n = 25]) can be divided into two major groups: a headache group (n = 12) and a normal pressure hydrocephalus (NPH)-symptom group (n = 11), Two patients had both headaches and NPH symptoms. The patients in the headache group were significantly younger and had smaller ventricles than the patients in the NPH group. With multivariate regression analysis, age independently affected the type of chronic symptoms. CONCLUSIONS: LIAS typically presents with chronic onset, with younger patients tending to have headaches, and older patients tending to have NPH symptoms. ETV is considered the best surgical option, with more than an 80% success rate.

Cerebrovascular adaptation in chronic hydrocephalus.

This study characterizes the regional changes in vascularity, which accompanies chronic progressive hydrocephalus. Fifteen dogs underwent surgical induction of hydrocephalus and were used for histologic studies. Animals were divided into 4 groups: surgical control, short term (< or = 5 weeks), intermediate term (8 weeks), and long term (10 to 12 weeks). Vessel diameter, density, and luminal area were calculated by imaging quantification after manual vessel identification in the cortical gray, white matter, and caudate nucleus. Capillary vessel diameter decreased 23.5% to 30.2% (P < 0.01) in the caudate, but then returned to normal at 12 weeks. Capillary vessel density decreased 53.5% (P < 0.05) in the cortical gray, but then increased to 234.8% (P < 0.01) over surgical controls at 12 weeks. There was no initial decrease in capillary density in the caudate; however, the long-term group capillary density was significantly greater (172.8% to 210.5%, P < 0.01) than surgical controls. Overall, there was a short-term decrease in lumen area, with recovery in the longer term. Glial fibrillary acidic protein (GFAP) immunohistochemistry demonstrated the pattern of GFAP staining and reactive astrocytes differed in the caudate compared with the occipital cortex. This data suggest that an increase in capillary density and diameter may be an adaptive process allowing maintenance of adequate cerebral perfusion and metabolic support in the hypoxic environment of chronic hydrocephalus.

Effects of ventriculoperitoneal shunt removal on cerebral oxygenation and brain compliance in chronic obstructive hydrocephalus.

OBJECT: The pathophysiology of shunt malfunction has not been fully examined, probably because of the paucity of appropriate animal models. Using a canine model of chronic obstructive hydrocephalus, the effects of shunt placement and removal on physiological parameters were evaluated. METHODS: Fifteen dogs, nine in which chronic hydrocephalus was induced and six controls, were used in the experiment. Thirteen weeks after the induction of hydrocephalus, intracranial pressure (ICP), tissue and cerebrospinal fluid O2 saturation, response to hyperventilation, and brain compliance at low (5-15 mm Hg) and high (15-25 mm Hg) pressures were measured (untreated stage). Following this procedure, ventriculoperitoneal shunts were implanted in the dogs suffering from hydrocephalus. Two weeks later, the same series of measurements were repeated (shunted stage), following which the shunt systems were removed. One week after shunt removal, the last measurements were obtained (shunt-removed stage). All dogs underwent magnetic resonance imaging four times: before induction of hydrocephalus and before each measurement. All dogs with hydrocephalus also had ventriculomegaly (1.42 +/- 0.89 ml before induction of hydrocephalus compared with 3.4 +/- 1.64 ml 13 weeks after induction, p = 0.0064). In dogs in the untreated hydrocephalus stage, ICP remained within the normal range (8.33 +/- 2.60 mm Hg)--although it was significantly higher than that in the control group (5 +/- 1.41 mm Hg, p = 0.014). Tissue O2 saturation in the dogs in the hydrocephalus group (26.1 +/- 5.33 mm Hg) was lower than that in the dogs in the control group (48.7 +/- 4.27 mm Hg, p < 0.0001). After the dogs underwent shunt placement, significant improvement was observed in their ICP (5.22 +/- 2.17 mm Hg, p = 0.012) and tissue O2 saturation (35.2 +/- 6.80 mm Hg, p = 0.0084). However, removal of the shunt reversed these improvements back to the preshunt status. Hyperventilation induced significant decreases in ICP and O2 saturation at every measurement time and induced a significant decrease in tissue O2 saturation during the shunted stage, but not during the untreated and shunt-removed stages. Brain compliance measured at high pressure demonstrated a significant gradual decrease at every measurement. CONCLUSIONS: In chronic obstructive hydrocephalus, shunt placement improves ICP and cerebral oxygenation as well as the response to hyperventilation in the tissue. Shunt removal reverses these improvements back to levels present during the untreated stage. The decrease in brain compliance may be one of the factors responsible for symptoms in shunt malfunction.

Quantifying muscle activity in non-ambulatory children with spastic cerebral palsy before and after selective dorsal rhizotomy.

Cerebral palsy is a condition that results in varying degrees of functional deficits. The goal of this study was to develop an objective measure of muscle activity during a prescribed voluntary motor task in non-ambulatory children with spastic cerebral palsy. While performing a simultaneous hip/knee flexion task from the supine position, followed by return to the starting position, electromyographic and kinematic data were obtained from the right leg of eight children before and after selective dorsal rhizotomy and compared with eight age-matched controls. The electromyographic and kinematic data were combined to determine for each muscle of interest (tibialis anterior, soleus, vastus lateralis, biceps femoris) the percentage of the movement cycle for which the muscle was acting concentrically, eccentrically, isometrically or was considered inactive. Averaged over the four muscles, isometric activity decreased by 38% post-op and the time the muscles were inactive increased by 37% following surgery. The percentages of concentric and eccentric activity did not differ significantly between pre- and post-op conditions. Post-operatively, the percentage muscle activity patterns of the children with cerebral palsy more closely resembled that of the control children: averaged across all muscles and contraction types, the difference between the control children and the children with cerebral palsy was reduced by 50% following surgery. This measurement technique indicates promise as a method for quantifying muscle activity during voluntary motor tasks in non-ambulatory children with cerebral palsy.

Functional magnetic resonance imaging before and after ventriculoperitoneal shunting for hydrocephalus--case report.

A 70-year-old man with hydrocephalus was examined with functional magnetic resonance (fMR) imaging before and after ventriculoperitoneal shunting. Preoperatively, activation by right hand exercise revealed only a slight signal increase in the peri-rolandic area. However, 3 months after ventriculoperitoneal shunting, a significant signal increase was observed. fMR imaging may detect activity-related improvement of cerebral blood flow responses in patients with hydrocephalus after surgical treatment.

Nerve rootlets to be sectioned for spasticity resolution in selective dorsal rhizotomy.

BACKGROUND: The goal of this study is to confirm the efficacy of the protocol for selective dorsal rhizotomy (SDR). In this protocol, rootlets to be sectioned are selected by palpable responses elicited by intraoperative electrical stimulation, without detailed electromyographic classifications. METHODS: Thirty-six children with spasticity due to cerebral palsy underwent SDR according to our protocol. Priority was given to sectioning rootlets that showed palpable clonic or bilateral responses, which were considered abnormal, over sectioning rootlets that merely had hyperactive responses to intraoperative stimulation. The results of intraoperative monitoring and sectioning amount were analyzed by physical evaluation. RESULTS: Significant improvements were obtained in passive range of motion and muscle tone of the lower extremities. The total percentages of rootlets with abnormal and hyperactive responses at L3 and S1 were bilaterally correlated with preoperative spasticity of the hip adductors and the plantar flexors, respectively. When rootlets with hyperactive responses were excluded from the correlation analysis, no bilateral correlation was observed. From the correlation analyses between the improvement in the physical evaluation and the amount of nerve sectioned, it was concluded that a greater improvement in muscle tone in all examined muscles, except the hamstrings, could be obtained if larger amounts of nerve roots were sectioned. CONCLUSION: The number of rootlets with palpable abnormal and hyperactive responses elicited by intraoperative stimulation reflects the preoperative spasticity of multiple muscles. This implies that only selecting rootlets with palpable responses can be reliable. Because more sectioning leads to better spasticity resolution, our protocol should be reviewed to increase the percentage of rootlets sectioned with hyperactive responses, especially for innervated levels of severely affected muscles.

Critical shunt-induced subdural hematoma treated with combined pressure-programmable valve implantation and endoscopic third ventriculostomy.

The authors present 2 patients with VP shunt-induced subdural hematomas (SDH) treated with pressure-programmable valve implantation and endoscopic third ventriculostomies (TV). The first patient is an 11-year-old girl who developed a shunt-induced SDH. Revision of the shunt valve with a higher-pressure valve resulted in a prolonged deterioration of her consciousness. External ventricular drainage at low pressure led to clinical improvement. A pressure-programmable valve set at 50 mm H(2)O was implanted, and the pressure gradually increased. At a pressure of 120 mm H(2)O symptoms recurred, even though the subdural collection was beginning to decrease in size. An endoscopic TV was performed, and the valve pressure was then increased to 200 mm H(2)O without any neurological symptoms. The second patient, a 7-year-old boy with shunt-induced SDH, had recurrent SDH, even after shunt revision with placement of a higher-pressure valve, which resulted in prolonged lethargy. A pressure-programmable valve was implanted with concurrent endoscopic TV. Gradual valve pressure increases up to 200 mm H(2)O could be performed without recurrent symptoms. Eventually, the shunt system was ligated to resolve residual positional headache, and the TV has been patent for more than 3 years. In both patients, the pressure-programmable valve was useful, since the optimal CSF drainage pressure changed during the period of recovery from symptomatic subdural collections. Concurrent TV appeared to enable increasing the valve pressure gradually without any neurological symptoms. The advantages of this combined approach are discussed.

Risk factors for failure of endoscopic third ventriculostomy for obstructive hydrocephalus.

OBJECTIVE: This is a retrospective study to identify risk factors for failure in the treatment of obstructive hydrocephalus with endoscopic third ventriculostomy (ETV). METHODS: The records for 89 patients, including 32 with ventriculoperitoneal or ventriculoatrial shunt malfunctions or infections, who underwent ETVs between 1993 and 1998, at our institution, were examined. Multiple variables possibly related to failure were considered. These included age, sex, cause of hydrocephalus, presence and function of ventriculoperitoneal/ventriculoatrial shunts, history of shunt revisions or infections, symptoms, preoperative imaging results, presence of retained shunt catheters, postoperative meningitis, and postoperative ventricular size. RESULTS: Twenty-nine patients (32.6%) required subsequent shunt replacement and/or ETV revision. Of these 29 reoperations, 12 procedures (41.4%) were performed within 2 weeks and only 3 were performed more than 10 months after the initial ETV procedure. The ventricular size remained unchanged in 75% of the cases on the day after ETV, in 57.4% at 3 months, in 48.2% at 6 months, and in 41.8% at 1 year. Cine phase-contrast magnetic resonance imaging findings were consistent with postoperative symptomatic resolution in 96.3% of the cases. Seven patients (7.9%) experienced complications related to ETV, all of which were transient. Significant risk factors in univariate analyses were as follows: presence of Chiari Type I malformation (P = 0.003), shunt infection at presentation (P = 0.014), history of shunt infections (P = 0.0004), three or more previous shunt revisions (P = 0.0018), and postoperative meningitis (P = 0.0001). Late-onset idiopathic aqueductal stenosis was a significant predictor of good outcomes (P = 0.044). These factors were reanalyzed in a multivariate analysis, which confirmed a history of shunt infections and postoperative meningitis as independent risk factors. CONCLUSION: The risk of failure increases with intracerebral infection, likely because of obliteration of cerebrospinal fluid pathways.

Third ventriculostomy patency: comparison of findings at cine phase-contrast MR imaging and at direct exploration.

BACKGROUND AND PURPOSE: Two-dimensional phase-contrast (PC) MR imaging is a known method for evaluating CSF flow after third ventriculostomy. In this study, we attempted to confirm the accuracy of cine PC MR imaging for determining the patency of a third ventriculostomy as compared with direct reexploration of the floor of the third ventricle. METHODS: We examined 11 patients with third ventriculostomies who had a total of 13 reoperations for symptomatic obstructive hydrocephalus. In 12 of the 13 reexplorations, cine PC MR studies were obtained before repeat surgery, and the diagnoses suggested by imaging were compared with intraoperative findings. RESULTS: Four of five patients who had no flow on MR images had new membranes that covered the orifice; the fifth patient still had a small perforation visible at the time of operation. Three of four patients who had subtle flow on MR images were found to have occlusion with new membranes; the fourth had an incomplete new membrane. Finally, two of three who had a patent ventriculostomy had completely open perforations without membrane formation; the third patient had nonobstructive early membrane formation. At 3 months' follow-up, two flow studies were read as subtle without any clinical symptoms; however, these eventually progressed to become symptomatic, and occlusion with new membrane formation was confirmed during surgical reexploration. CONCLUSION: Cine PC MR imaging is a reliable technique for detecting the patency of a third ventriculostomy, but minor flow, as defined in this report, appears to be an early sign of closure.

Development and characterization of an adult model of obstructive hydrocephalus.

While hydrocephalus is common in adults its pathophysiology is not fully understood and its treatment remains problematic. Previous animal models have been acute, developmental, or involved non-specific blockage or inflammation and are not suitable for study of chronic adult-onset hydrocephalus. In this study, we describe the development of a canine model which allows basic physiological studies along with diagnostic and treatment procedures via surgical occlusion of the fourth ventricle with a bolus injection of cyanoacrylic gel glue. A total of 26 adult male canine mongrels were used for the induction of chronic hydrocephalus and were monitored for 1-12 weeks post-induction using magnetic resonance imaging (MRI), intracranial pressure measurements, and neurological fitness assessments. Of these, 81% (21/26) developed hydrocephalus that was mild (N = 6), moderate (N = 7), or severe (N = 8). Pressures were mild and transiently elevated, and brain compliance decreased. Clinical symptoms were also mild and transient. This model is unique in its focal obstruction without local compression or general inflammation and should facilitate the study of the pathophysiology and treatment of chronic adult-onset hydrocephalus.

Ocular malformations, moyamoya disease, and midline cranial defects: a distinct syndrome.

PURPOSE: To report a 10-year-old girl with developmental anomalies of both optic disks, a chorioretinal coloboma, sphenopharyngeal meningoencephalocele, and moyamoya disease. METHODS: A full ophthalmologic examination, cranial magnetic resonance imaging and magnetic resonance angiography, and cerebral angiography were performed. RESULTS: The patient had a morning glory disk anomaly and microphthalmos of the right eye and optic nerve hypoplasia and retinochoroidal coloboma in the left eye. She had a midfacial cleft and an episode of seizures and a stroke. Magnetic resonance imaging showed a sphenopharyngeal meningoencephalocele. Magnetic resonance angiography and cerebral angiography demonstrated a pattern consistent with moyamoya disease. CONCLUSIONS: This patient had a distinct syndrome of optic disk, retinochoroidal, and carotid circulation anomalies with midline cranial defects. The recognition and treatment of the vascular abnormalities and cranial defects may prevent complications such as strokes that may occur during or after general anesthesia.

Decreased c-fos expression in experimental neonatal hydrocephalus: evidence for reduced neuronal activation.

Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a "third messenger" to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.