Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document.

BACKGROUND: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. METHODS: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). RESULTS: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." CONCLUSIONS: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.

Neurodevelopmental profile in children with benign external hydrocephalus syndrome. A pilot cohort study.

PURPOSE: The management of children with benign external hydrocephalus (BEH) remains controversial. Most BEH children do well in the long-term, but a substantial number have temporary or permanent psychomotor delays. The study aims to assess the prevalence and pattern of neurodevelopmental delay in a cohort of children with BEH. METHODS: We conducted a cohort study of 42 BEH children (30 boys and 12 girls, aged 6 to 38 months). A pediatric neurosurgeon performed a first clinical evaluation to confirm/reject the diagnosis according to the clinical features and neuroimaging studies. Two trained evaluators assessed the child's psychomotor development using the third edition of the Bayley Scales of Infant and Toddler Development (Bayley-III). Developmental delay was defined as a scaled score < 7 according to the simple scale and/or a composite score < 85. RESULTS: Eighteen children (43%) presented statistically lower scores in the gross motor and composite motor of the Bayley-III scales compared to their healthy peers. CONCLUSION: In BEH, it is important to establish a diagnostic algorithm that helps to discriminate BEH patients that have self-limiting delays from those at risk of a persistent delay that should be referred for additional studies and/or interventions that might improve the natural evolution of a disease with high impact on the children and adult's quality of life.

CO2-induced intracranial hypertension and high-amplitude B-waves in a patient with Chiari 1 malformation and sleep apnea syndrome that resolved following CPAP therapy.

Headaches and cognitive impairment in the elderly population have been described as symptoms related to obstructive sleep apnea (OSA). Although papilledema has been observed in some of these patients, suggesting intracranial hypertension (ICH), there are only a few studies in which intracranial pressure (ICP) has been continuously measured in patients with OSA without neurological disease. We present a patient diagnosed with Chiari Type 1 malformation and OSA, who present normal ICP recording during the day and nocturnal ICH associated with high amplitude B-waves and hypercapnia during obstructive apneas, which disappeared following continuous positive airway pressure (CPAP) therapy. The normalization of the cerebral and respiratory parameters with CPAP therapy is important for performing the correct treatment in these patients.

Distal catheter lengthening in pediatric patients with hydrocephalus using a guidewire-assisted technique.

PURPOSE: The aim of this study was to evaluate the lengthening or replacement of the peritoneal catheter in a ventriculoperitoneal shunt by using a simple guidewire-assisted technique. Here we report on our experience with this methodology, its indications, caveats, and contraindications. METHODS: A prospective study was performed in 59 consecutively shunted children who required elective lengthening of the peritoneal catheter (25 females and 34 males, mean 10.5 + 4.2 years). The procedure required an incision of only 1 cm over the distal catheter. The catheter was sectioned, and a soft hydrophilic guidewire was inserted into the exposed end of it, which serves as a route for the guidewire to reach the intraperitoneal space. The procedure was followed by the replacement of the patient's catheter with one with additional length as considered appropriate, prior to putting additional slots in the last 5 to 8 cm of the new catheter. RESULTS: The technique was used in 62 CSF shunts (3 patients had a double derivative system). Fifty-five of the 62 (89%) procedures performed were effective. A conventional peritoneal opening technique was used in the 7 unsuccessful attempts. One patient presented a migration of the abdominal catheter during the first days after surgery. No incident of peritoneal perforation was associated with this technique, nor were any infections or other early or late complications associated with this surgical procedure. CONCLUSION: The technique we propose permits the peritoneal catheter of a derivative system to be lengthened or replaced in a manner that is simple, fast, and safe.

Target location after deep cerebral biopsies using low-volume air injection in 75 patients. Results and technical note.

BACKGROUND: Stereotactic biopsy is a minimally invasive technique that allows brain tissue samples to be obtained with low risk. Classically, different techniques have been used to identify the biopsy site after surgery. OBJECTIVE: To describe a technique to identify the precise location of the target in the postoperative CT scan using the injection of a low volume of air into the biopsy cannula. METHODS: Seventy-five biopsies were performed in 65 adults and 10 children (40 males and 35 females, median age 51 years). Frame-based biopsy was performed in 46 patients, while frameless biopsy was performed in the remaining 29 patients. In both systems, after brain specimens had been collected and with the biopsy needle tip in the center of the target, a small volume of air (median 0.7 cm3) was injected into the site. RESULTS: A follow-up CT scan was performed in all patients. Intracranial air in the selected target was present in 69 patients (92%). No air was observed in two patients (air volume administered in these 2 cases was below 0.7 cm3), while in the remaining four patients blood content was observed in the target. The diagnostic yield in this series was 97.3%. No complications were found to be associated with intracranial air injection in any of the 75 patients who underwent this procedure. CONCLUSIONS: The air-injection maneuver proposed for use in stereotactic biopsies of intracranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications.

Surgical Outcomes in Chiari 1 and Chiari 1.5 Malformation Treated by Posterior Fossa Reconstruction: A Comprehensive Analysis of 110 Pediatric Cases and Literature Review.

Background/Objectives: The management of Chiari malformations (CMs) remains a clinical challenge and a topic of great controversy. Results may vary between children and adults. The purpose of the current single-center study is to critically assess the one-year surgical outcomes of a cohort of 110 children with CM-1 or CM-1.5 who were treated using "posterior fossa reconstruction" (PFR), a surgical technique described in 1994 that has since been used in both adults and children. We also review the literature and discuss the possible causes of the drawbacks and pitfalls in children in whom PFR was ineffective in controlling the disease. Methods: The present cohort was selected from a prospective registry of adults and children with CMs collected since 2006. Patients included in this study were selected from a group of children with CMs who were operated on in our Pediatric Neurosurgical Unit between 1 January 2007 and 31 November 2023. Surgical outcome was defined based on clinical and neuroradiological results as very good, good, or bad. Results: The mean age of our child cohort was 9.9 ± 4.7 years, with 54 girls (49%) and 56 boys (51%). Sixty-six children had CM-1 (60%) while forty-four had CM-1.5 (40%). Following surgery, there was no neurological worsening or death among the children. Most children (70%) had an uneventful recovery and were discharged home on average one week after surgery. However, in 33 children (30%), we recorded at least one postoperative adverse event. Aseptic meningitis syndrome was the most frequent adverse event (n = 25, 22.7%). The final surgical outcome was evaluated one year after PFR by using both clinical and neuroradiological results. The one-year surgical outcome was excellent in 101 children (91.9%), good in 5 (4.5%), and bad in 4 (3.6%). Conclusions: PFR significantly enlarges the volume of the posterior fossa and recreates a CSF environment that generates buoyancy of the cerebellum, with a high percentage of excellent and good clinical results evaluated one year post-surgery.

How the heterogeneity of the severely injured brain affects hybrid diffuse optical signals: case examples and guidelines.

Significance: A shortcoming of the routine clinical use of diffuse optics (DO) in the injured head has been that the results from commercial near-infrared spectroscopy-based devices are not reproducible, often give physiologically invalid values, and differ among systems. Besides the limitations due to the physics of continuous-wave light sources, one culprit is the head heterogeneity and the underlying morphological and functional abnormalities of the probed tissue. Aim: The aim is to investigate the effect that different tissue alterations in the damaged head have on DO signals and provide guidelines to avoid data misinterpretation. Approach: DO measurements and computed tomography scans were acquired on brain-injured patients. The relationship between the signals and the underlying tissue types was classified on a case-by-case basis. Results: Examples and suggestions to establish quality control routines were provided. The findings suggested guidelines for carrying out DO measurements and speculations toward improved devices. Conclusions: We advocate for the standardization of the DO measurements to secure a role for DO in neurocritical care. We suggest that blind measurements are unacceptably problematic due to confounding effects and care using a priori and a posteriori quality control routines that go beyond an assessment of the signal-to-noise ratio that is typically utilized.

Brain activation during speech perception in a patient with a massive left hemisphere infarction.

BACKGROUND: Little is known about the regions involved in recovery from global aphasia in patients with malignant infarction after decompressive hemicraniectomy. This study reports a case of brain activation during speech perception in a right-handed patient with a massive left hemispheric infarction. METHODS: Decompressive hemicraniectomy was performed in a 20-year old woman with space-occupying infarction of the speech dominant hemisphere. Complete anterior, middle and part of the posterior cerebral artery territories of the left hemisphere, as well as posterior regions of the right middle cerebral artery territory, were affected. Neuropsychological testing and functional magnetic resonance imaging (fMRI) during speech perception were performed 10 months after stroke. RESULTS: The patient was able to walk, go up and down stairs independently and perform simple tasks at home. She was also well able to match visually and orally presented words with their corresponding pictures, despite large bilateral lesions in the posterior regions. fMRI revealed strong activation of the left temporo-occipital and parieto-occipital areas. In the right hemisphere was observed a small area of activation in the posterior part of the superior and middle temporal gyrus. CONCLUSIONS: In aphasic patients, the activation of posterior bilateral associative areas might be used to support language perception.

The Role of Neurophysiology in Managing Patients with Chiari Malformations.

Chiari malformation type 1 (CM1) includes various congenital anomalies that share ectopia of the cerebellar tonsils lower than the foramen magnum, in some cases associated with syringomyelia or hydrocephalus. CM1 can cause dysfunction of the brainstem, spinal cord, and cranial nerves. This functional alteration of the nervous system can be detected by various modalities of neurophysiological tests, such as brainstem auditory evoked potentials, somatosensory evoked potentials, motor evoked potentials, electromyography and nerve conduction studies of the cranial nerves and spinal roots, as well as brainstem reflexes. The main goal of this study is to review the findings of multimodal neurophysiological examinations in published studies of patients with CM1 and their indication in the diagnosis, treatment, and follow-up of these patients, as well as their utility in intraoperative monitoring.

A Critical Update of the Classification of Chiari and Chiari-like Malformations.

Chiari malformations are a group of craniovertebral junction anomalies characterized by the herniation of cerebellar tonsils below the foramen magnum, often accompanied by brainstem descent. The existing classification systems for Chiari malformations have expanded from the original four categories to nine, leading to debates about the need for a more descriptive and etiopathogenic terminology. This review aims to examine the various classification approaches employed and proposes a simplified scheme to differentiate between different types of tonsillar herniations. Furthermore, it explores the most appropriate terminology for acquired herniation of cerebellar tonsils and other secondary Chiari-like malformations. Recent advances in magnetic resonance imaging (MRI) have revealed a higher prevalence and incidence of Chiari malformation Type 1 (CM1) and identified similar cerebellar herniations in individuals unrelated to the classic phenotypes described by Chiari. As we reassess the existing classifications, it becomes crucial to establish a terminology that accurately reflects the diverse presentations and underlying causes of these conditions. This paper contributes to the ongoing discussion by offering insights into the evolving understanding of Chiari malformations and proposing a simplified classification and terminology system to enhance diagnosis and management.

Erratum: Transcranial optical monitoring for detecting intracranial pressure alterations in children with benign external hydrocephalus: a proof-of-concept study.

[This corrects the article DOI: 10.1117/1.NPh.9.4.045005.].

Preterm birth and early life environmental factors: neuropsychological profiles at adolescence and young adulthood.

OBJECTIVES: To establish neuropsychological profiles after high- and low-risk preterm birth (i.e., with and without neonatal brain injury) during adolescence and young adulthood and to assess the potential role of early life environmental factors in cognition. STUDY DESIGN: Participants (N = 177; Mage = 20.11 years) of both sexes were evaluated when adolescent or in young adulthood. They were grouped according to their birth status: 30 high-risk preterm, 83 low-risk preterm and 64 born at full term. RESULTS: Significant differences were found in several cognitive domains between groups. Furthermore, familial socioeconomic status (SES) moderated the relation between the degree of maturity/immaturity at birth and cognition (F(5,171) = 11.94, p < 0.001, R2 = 0.26). DISCUSSION: The findings showed different neuropsychological profiles during adolescence and young adulthood, with the high-risk preterm sample evidencing lower cognitive values. In addition, higher scores in the familial SES score in this study seem to have a protective effect on cognition.

Comparison of cerebral metabolic rate of oxygen, blood flow, and bispectral index under general anesthesia.

Significance: The optical measurement of cerebral oxygen metabolism was evaluated. Aim: Compare optically derived cerebral signals to the electroencephalographic bispectral index (BIS) sensors to monitor propofol-induced anesthesia during surgery. Approach: Relative cerebral metabolic rate of oxygen ( rCMRO 2 ) and blood flow (rCBF) were measured by time-resolved and diffuse correlation spectroscopies. Changes were tested against the relative BIS (rBIS) ones. The synchronism in the changes was also assessed by the R-Pearson correlation. Results: In 23 measurements, optically derived signals showed significant changes in agreement with rBIS: during propofol induction, rBIS decreased by 67% [interquartile ranges (IQR) 62% to 71%], rCMRO 2 by 33% (IQR 18% to 46%), and rCBF by 28% (IQR 10% to 37%). During recovery, a significant increase was observed for rBIS (48%, IQR 38% to 55%), rCMRO 2 (29%, IQR 17% to 39%), and rCBF (30%, IQR 10% to 44%). The significance and direction of the changes subject-by-subject were tested: the coupling between the rBIS, rCMRO 2 , and rCBF was witnessed in the majority of the cases (14/18 and 12/18 for rCBF and 19/21 and 13/18 for rCMRO 2 in the initial and final part, respectively). These changes were also correlated in time ( R > 0.69 to R = 1 , p - values < 0.05 ). Conclusions: Optics can reliably monitor rCMRO 2 in such conditions.

Intraoperative Neurophysiological Monitoring in Syringomyelia Surgery: A Multimodal Approach.

Syringomyelia can be associated with multiple etiologies. The treatment of the underlying causes is first-line therapy; however, a direct approach to the syrinx is accepted as rescue treatment. Any direct intervention on the syrinx requires a myelotomy, posing a significant risk of iatrogenic spinal cord (SC) injury. Intraoperative neurophysiological monitoring (IONM) is crucial to detect and prevent surgically induced damage in neural SC pathways. We retrospectively reviewed the perioperative and intraoperative neurophysiological data and perioperative neurological examinations in ten cases of syringomyelia surgery. All the monitored modalities remained stable throughout the surgery in six cases, correlating with no new postoperative neurological deficits. In two patients, significant transitory attenuation, or loss of motor evoked potentials (MEPs), were observed and recovered after a corrective surgical maneuver, with no new postoperative deficits. In two cases, a significant MEP decrement was noted, which lasted until the end of the surgery and was associated with postoperative weakness. A transitory train of neurotonic electromyography (EMG) discharges was reported in one case. The surgical plan was adjusted, and the patient showed no postoperative deficits. The dorsal nerve roots were stimulated and identified in the seven cases where the myelotomy was performed via the dorsal root entry zone. Dorsal column mapping guided the myelotomy entry zone in four of the cases. In conclusion, multimodal IONM is feasible and reliable and may help prevent iatrogenic SC injury during syringomyelia surgery.

Transcranial optical monitoring for detecting intracranial pressure alterations in children with benign external hydrocephalus: a proof-of-concept study.

Significance: Benign external hydrocephalus (BEH) is considered a self-limiting pathology with a good prognosis. However, some children present a pathological intracranial pressure (ICP) characterized by quantitative and qualitative alterations (the so-called B-waves) that can lead to neurological sequelae. Aim: Our purpose was to evaluate whether there were cerebral hemodynamic changes associated with ICP B-waves that could be evaluated with noninvasive neuromonitoring. Approach: We recruited eleven patients (median age 16 months, range 7 to 55 months) with BEH and an unfavorable evolution requiring ICP monitoring. Bedside, nocturnal monitoring using near-infrared time-resolved and diffuse correlation spectroscopies synchronized to the clinical monitoring was performed. Results: By focusing on the timing of different ICP patterns that were identified manually by clinicians, we detected significant tissue oxygen saturation ( StO 2 ) changes ( p = 0.002 ) and blood flow index (BFI) variability ( p = 0.005 ) between regular and high-amplitude B-wave patterns. A blinded analysis looking for analogs of ICP patterns in BFI time traces achieved 90% sensitivity in identifying B-waves and 76% specificity in detecting the regular patterns. Conclusions: We revealed the presence of StO 2 and BFI variations-detectable with optical techniques-during ICP B-waves in BEH children. Finally, the feasibility of detecting ICP B-waves in hemodynamic time traces obtained noninvasively was shown.

Considerations in the Use of Gravitational Valves in the Management of Hydrocephalus. Some Lessons Learned with the Dual-Switch Valve.

In the past decade, there has been a clear trend towards better outcomes in patients with hydrocephalus, especially those with normal pressure hydrocephalus (NPH). This is partly due to the availability of more sophisticated hardware and a better understanding of implants. However, there is little evidence to show the superiority of a specific type of valve over another. The most commonly reported consequence of hydrodynamic mismatch is shunt over-drainage. Simple differential pressure valves, with a fixed opening pressure or even adjustable valves, lead to non-physiologic intraventricular pressure (IVP) as soon as the patient moves into an upright posture. These valves fail to maintain IVP within physiological limits due to the changes in hydrostatic pressure in the drainage system. To solve this problem more complex third-generation hydrostatic valves have been designed. These gravitational devices aim to reduce flow through a shunt system when the patient is upright but there are important technical differences between them. Here we review the main characteristics of the Miethke® Dual-Switch valve, which includes two valve chambers arranged in parallel: a low-opening pressure valve, designed for working in the supine position, and a second high-opening pressure valve, which starts working when the patient assumes the upright position. This paper specifies the main advantages and drawbacks of this device and provide a series of recommendations for its use. The discussion of this specific gravitational valve allows us to emphasize the importance of using gravitational control in implanted shunts and some the caveats neurosurgeons should take into consideration when using gravitational devices in patients with hydrocephalus. The correct function of any gravitational device depends on adequate device implantation along the vertical body axis. Misalignment from the vertical axis equal to or more than 45° might eliminate the beneficial effect of these devices.

Cortical Spreading Depression Phenomena Are Frequent in Ischemic and Traumatic Penumbra: A Prospective Study in Patients With Traumatic Brain Injury and Large Hemispheric Ischemic Stroke.

PURPOSE: Spreading depolarization (SD) phenomena are waves of neuronal depolarization, which propagate slowly at a velocity of 1 to 5 mm/minute and can occur in patients with ischemic or hemorrhagic stroke, traumatic brain injury, and migraine with aura. They form part of secondary injury, occurring after spreading ischemia. The purposes of this study were to describe the frequency and characteristics of SD phenomena and to define whether a correlation existed between SD and outcome in a group of patients with TBI and large hemispheric ischemic stroke. METHODS: This was a prospective observational study of 39 adult patients, 17 with malignant middle cerebral artery infarction and 22 with moderate or severe traumatic brain injury, who underwent decompressive craniectomy and multimodal neuromonitoring including electrocorticography. Identification, classification, and interpretation of SDs were performed using the published recommendations from the Cooperative Study on Brain Injury Depolarization group. The outcomes assessed were functional disability at 6 and 12 months after injury, according to the extended Glasgow outcome scale, Barthel index, and modified Rankin scale. RESULTS: Four hundred eighty-three SDs were detected, in 58.9% of the patients. Spreading depolarizations were more common, particularly the isoelectric SD type, in patients with malignant middle cerebral artery infarction (P < 0.04). In 65.21% of patients with SDs on electrocorticography, the "peak" day of depolarization was day 0 (the first 24 hours of recording). Spreading depolarization convulsions were present in 26.08% of patients with SDs. Patients with more SDs and higher depolarization indices scored worse on extended Glasgow outcome scale (6 months) and Barthel index (6 and 12 months) (P < 0.05). CONCLUSIONS: Evidence on SD phenomena is important to ensure continued progress in understanding their pathophysiology, in the search for therapeutic targets to avoid additional damage from these secondary injuries.

Rare functional genetic variants in COL7A1, COL6A5, COL1A2 and COL5A2 frequently occur in Chiari Malformation Type 1.

Chiari Malformation Type 1 (CM-1) is characterized by herniation of the cerebellar tonsils below the foramen magnum and the presence of headaches and other neurologic symptoms. Cranial bone constriction is suspected to be the most common biologic mechanism leading to CM-1. However, other mechanisms may also contribute, particularly in the presence of connective tissue disorders (CTDs), such as Ehlers Danlos Syndrome (EDS). Accumulating data suggest CM-1 with connective tissue disorders (CTD+) may have a different patho-mechanism and different genetic risk factors than CM-1 without CTDs (CTD-). To identify CM-1 genetic risk variants, we performed whole exome sequencing on a single large, multiplex family from Spain and targeted sequencing on a cohort of 186 unrelated adult, Caucasian females with CM-1. Targeted sequencing captured the coding regions of 21 CM-1 and EDS candidate genes, including two genes identified in the Spanish family. Using gene burden analysis, we compared the frequency of rare, functional variants detected in CM-1 cases versus publically available ethnically-matched controls from gnomAD. A secondary analysis compared the presence of rare variants in these genes between CTD+ and CTD- CM-1 cases. In the Spanish family, rare variants co-segregated with CM-1 in COL6A5, ADGRB3 and DST. A variant in COL7A1 was present in affected and unaffected family members. In the targeted sequencing analysis, rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls. In total, 47% of CM-1 cases presented with rare variants in at least one of the four significant collagen genes and 10% of cases harbored variants in multiple significant collagen genes. Moreover, 26% of CM-1 cases presented with rare variants in the COL6A5 gene. We also identified two genes (COL7A1, COL3A1) for which the burden of rare variants differed significantly between CTD+ and CTD- CM-1 cases. A higher percentage of CTD+ patients had variants in COL7A1 compared to CTD+ patients, while CTD+ patients had fewer rare variants in COL3A1 than did CTD- patients. In summary, rare variants in several collagen genes are particularly frequent in CM-1 cases and those in COL6A5 co-segregated with CM-1 in a Spanish multiplex family. COL6A5 has been previously associated with musculoskeletal phenotypes, but this is the first association with CM-1. Our findings underscore the contribution of rare genetic variants in collagen genes to CM-1, and suggest that CM-1 in the presence and absence of CTD symptoms is driven by different genes.

Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix-intraventricular hemorrhage.

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term effects that GM-IVH have on hippocampal subfields, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced significantly lower total hippocampal volumes bilaterally and hippocampal subfield volumes compared to both low-risk preterm and full-term groups. Finally, significant positive correlations between memory and hippocampal subfield volumes were only found in preterm participants together; memory and the right CA-field correlation remained significant after Bonferroni correction was applied (p = .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifically related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-field volume and memory during childhood.

To Shunt or Not to Shunt Patients with Idiopathic Normal Pressure Hydrocephalus? A Reappraisal of an Old Question.

The possibility that the cerebral ventricles can dilate without any increase in the pressure of the cerebrospinal fluid (CSF) was recognized in 1935 by Penfield who reported a patient in whom "…the cerebrospinal fluid spaces are closed and the ventricles progressively enlarge without the measured intraventricular pressure rising above 150 to 200 mm of water" [...].