CSF Upward Motion Is Crucial for ETV Success

Purpose: ETV is indicated for treating obstructions of major CSF pathways. The outcome evaluation often yields success rates of only +- 70% for shunt independency. Hence, compromised CSF absorption seems to occur more often than expected. We searched for parameters suitable to assess the involved CSF dynamics. Material and Methods: This was a prospective study in 58 paediatric patients (7.7 yrs. mean age) between 2000 and 2020 with aqueductal stenosis (11/58), obstruction of the aqueduct due to tumor growth (22/58),and connatal hydrocephalus (9/58). The average follow-up interval was 4.7 years. Head circumferences, Evans- and fronto-occipital horn ratios before and 3 months after ETV were obtained as Delta-indices. Furthermore ETV success score (ETVSS), the patency of the aqueduct pre- and postoperatively as well as of the stoma were assessed by flow void signs on MRI. Evaluation on MRI also included the shape of the floor of the 3rd ventricle and whether or not the septum pellucidum showed signs of perforation. Four patients were analysed pre- and postoperatively via real-time MRI. At least the educational status regarding protected or unprotected education was analyzed. Results:The prevalence of a bowing of the floor of the 3rd ventricle was 72%, and the ETVSS was 71.0%. In 26 children a septal perforations or an open aqueduct prior to ETV (19) could be identified. Mean ER and FOHR were reduced by 0.03 and 0.05 , respectively. Maintained open (flow void on postop MRI) or perforation could successfully be carried out during endoscopic surgery in 44 patients (79%). The disproportionate increase of head circumference abated in 79.4% of patients. New shunt insertion occurred in 16 patients (27.5%). Intraoperatively upward CSF flow was detected in all cases. Statistical analyses(ANOVA) showed significant results for unprotected education, postoperative ER and FOHR but not for open stoma. Conclusion: The identification of flow through the stoma on postoperative MRI seems to be a necessary but not sufficient condition for ETV success. In our study, ventricular volumes were used as parameters to determine success rates as well as unprotected education. Furthermore, enabling upward CSF flow driven by inspiration seems crucial for successful ETV.

Comparative anatomy of dissected optic lobes, optic ventricles, midbrain tectum, collicular ventricles, and aqueduct: evolutionary modifications as potential explanation for non-tumoral aqueductal anomalies in humans

Purpose An extensive literature has postulated multiple etiologies for aqueductal stenosis. No publications were found, discussing that evolutionary modifications might explain aqueductal anomalies. This study’s objectives were to review the evolutionary modifications of vertebrates’ tectum structures that might explain human aqueduct anomalies. Undertaking vertebrate comparative study is currently not feasible in view of limitations in obtaining vertebrate material. Thus, vertebrate material collected, injected, dissected, and radiographed in the early 1970s was analyzed, focusing on the aqueduct and components of the midbrain tectum. Methods Photographs of brain dissections and radiographs of the cerebral ventricles and arteries of adult shark, frog, iguana, rabbit, cat, dog, and primate specimens, containing a barium-gelatin radiopaque compound, were analyzed focusing on the aqueduct, the optic ventricles, the quadrigeminal plate, and collicular ventricles. The anatomic information provided by the dissections and radiographs is not reproducible by any other radiopaque contrast currently available. Results Dissected and radiographed cerebral ventricular and arterial systems of the vertebrates demonstrated midbrain tectum changes, including relative size modifications of the mammalian components of the tectum, simultaneously with the enlargement of the occipital lobe. There is a transformation of pre-mammalian optic ventricles to what appear to be collicular ventricles in mammals, as the aqueduct and collicular ventricle form a continuous cavity. Conclusions The mammalian tectum undergoes an evolutionary cephalization process consisting of relative size changes of the midbrain tectum structures. This is associated with enlargement of the occipital lobe, as part of overall neocortical expansion. Potentially, aqueductal anomalies could be explained by evolutionary modifications.

Diagnostic accuracy of sagittal TSE-T2W, variable flip angle 3D TSE-T2W and high-resolution 3D heavily T2W sequences for the stenosis of two localizations: the cerebral aqueduct and the superior medullary velum

Objectives: This study aimed to investigate the accuracy of conventional sagittal turbo spin echo T2-weighted (Sag TSE-T2W), variable flip angle 3D TSE (VFA-3D-TSE) and high-resolution 3D heavily T2W (HR-3D-HT2W) sequences in the diagnosis of primary aqueductal stenosis (PAS) and superior medullary velum stenosis (SMV-S), and the effect of stenosis localization on diagnosis. Methods: Seventy-seven patients were included in the study. The diagnosis accuracy of the HR-3D-HT2W, Sag TSE-T2W and VFA-3D-TSE sequences, was classified into three grades by two experienced neuroradiologists: grade 0 (the sequence has no diagnostic ability), grade 1 (the sequence diagnoses stenosis but does not show focal stenosis itself or membrane formation), and grade 2 (the sequence makes a definitive diagnosis of stenosis and shows focal stenosis itself or membrane formation). Stenosis localizations were divided into three as Cerebral Aquaduct (CA), superior medullary velum (SMV) and SMV+CA. In the statistical analysis, the grades of the sequences were compared without making a differentiation based on localization. Then, the effect of localization on diagnosis was determined by comparing the grades for individual localizations. Results: In the sequence comparison, grade 0 was not detected in the VFA-3D-TSE and HR-3D-HT2W sequences, and these sequences diagnosed all cases. On the other hand, 25.4% of grade 0 was detected with the Sag TSE-T2W sequence (P<0.05). Grade 1 was detected by VFA-3D-TSE in 23% of the cases, while grade 1 (12.5%) was detected by HRH-3D-T2W in only one case, and the difference was statistically significant (P<0.05). When the sequences were examined according to localizations, the rate of grade 0 in the Sag TSE-T2W sequence was statistically significantly higher for the SMV localization (33.3%) compared to CA (66.7%) and SMV+CA (0%) (P<0.05). Localization had no effect on diagnosis using the other sequences. Conclusion: In our study, we found that the VFA-3D-TSE and HR-3D-HT2W sequences were successful in the diagnosis of PAS and SMV-S contrary to the Sag TSE-T2W sequence.

Endoscopic third ventriculostomy in the treatment of hydrocephalus: A 20-year retrospective analysis of 209 consecutive cases

Background: Endoscopic third ventriculostomy (ETV) has been shown to be a sufficient alternative to shunts in surgical treatment of obstructive hydrocephalus. Long-term failure, age limitations, and outcome by cause are some of the issues debated in literature. The objective of this article is to analyze the clinical success and failure of ETV and its main complications. Methods: A total of 209 patients with hydrocephalus were submitted to ETV, including a mixed population of children and adults (from 0 to 59 years). Patients were divided into five groups: A – tumors, B – aqueductal stenosis, C – myelomeningocele, D – infection and hemorrhage, and E – arachnoid cyst. Variables were analyzed: age, ETV success rate, cerebrospinal fluid (CSF) fistula, mortality, and complications. Results: The two main causes of hydrocephalus were tumors (44.9%) and aqueductal stenosis (25.3%). The overall success rate was of 82.8%, and patients in Group E had the highest rate 90.9%. Group A had a success rate of 89.3%, and Group B had a rate of 88.6%. The ETV success rate was significantly higher in patients older than 1 year (P < 0.001); the former also had a lower risk of CSF fistula (P < 0.0001). The overall mortality rate was 2.8%. Conclusion: Better results were observed in the groups of patients with tumors, aqueductal stenosis, and arachnoid cysts, while those whose primary causes of hydrocephalus were myelomeningocele, infections, or bleeding had higher rates of failure after the procedure. This study demonstrated that age under 1 year and hydrocephalus caused by myelomeningocele, bleeding, and infection were considered independent risk factors of poor prognosis in ETV.

Case report: Flattening of the tectal plate in obstructive hydrocephalus with auto-ventriculostomy

Background Obstructive hydrocephalus in adulthood can be caused by stenosis in the aqueductal area. Chronic changes lead to a dilatation of the lateral ventricles and ballooning of infratentorial recesses. In rare cases a rupture of the floor of the third ventricle (so-called spontaneous ventriculostomy) has been described in the literature. Case presentation: We present two cases of chronic obstructive hydrocephalus due to aqueductal stenosis in adult patients. Magnetic resonance imaging included phase-contrast-imaging and revealed significant flow through the floor of the third ventricle in keeping with spontaneous ventriculostomy. In addition to other typical changes associated with chronic hydrocephalus, a distinct flattening of the tectal plate could be identified in one case. Conclusion We present two cases of spontaneous ventriculostomy in patients with chronic hydrocephalus. To our knowledge, flattening of the tectal plate has not yet been described in the literature and may be caused by continuous cerebrospinal fluid-pulsation.

Neuroophthalmological manifestations of congenital aqueductal stenosis

OBJECTIVE Congenital aqueductal stenosis (CAS) is a common etiology of hydrocephalus that occurs in a subset of infants and may be linked to an increased incidence of ophthalmological abnormalities and delayed developmental milestones. Although hydrocephalus is common and widely studied, sparse literature exists on patients with isolated (no identifiable genetic link) CAS along with analysis of ophthalmological manifestations. In this study, the authors sought to describe the ophthalmological abnormalities and delayed developmental milestones of patients with isolated CAS. METHODS Data of patients with CAS were prospectively entered and monitored in a surgical database maintained by the Department of Neurological Surgery at Children’s Hospital of Pittsburgh from January 2005 to October 2016. Patients with a family history of congenital hydrocephalus, positive testing for genetic forms of aqueductal stenosis, other congenital abnormalities suggesting an underlying genetic syndrome, and stenosis/obstruction due to secondary causes were excluded from this study. Prenatal and perinatal history, CSF diversion history, and a variety of outcomes, including ophthalmological deficits and developmental milestones, were collected and analyzed. RESULTS A total of 41 patients with isolated CAS were identified, with a mean follow-up duration of 6 years. Among that cohort, 26 patients (63.4%) developed neuroophthalmological complications, which were further stratified. Fourteen patients (34.1%) developed strabismus and 11 (26.8%) developed astigmatism, and 1 patient (2.4%) with papilledema was recorded. Among patients with ophthalmological abnormalities, 76.9% had delayed developmental milestones (p = 0.045). CONCLUSIONS Patients with CAS were found to have increased risk of ophthalmological abnormalities requiring correction, along with an increased risk of delayed developmental milestones. Importantly, there was a significant correlation between the development of ophthalmological abnormalities and delayed developmental milestones that was independent of CSF diversion history. Larger patient cohort studies are required to explore whether earlier development of hydrocephalus, as is the case in CAS, causes elevated rates of neurological and ophthalmological complications, and if earlier CSF diversion correlates with improved outcomes.

Intracranial pressure waveform characteristics in idiopathic normal pressure hydrocephalus and late-onset idiopathic aqueductal stenosis

Background Idiopathic normal pressure hydrocephalus (iNPH) and late-onset idiopathic aqueductal stenosis (LIAS) are two forms of chronic adult hydrocephalus of different aetiology. We analysed overnight intracranial pressure (ICP) monitoring to elucidate ICP waveform changes characteristic for iNPH and LIAS to better understand pathophysiological processes of both diseases. Methods 98 patients with iNPH and 14 patients with LIAS from two neurosurgical centres were included. All patients underwent diagnostic overnight computerised ICP monitoring with calculation of mean ICP, ICP heartbeat related pulse wave amplitude calculated in the frequency domain (AMP) and the time domain (MWA), index of cerebrospinal compensatory reserve (RAP) and power of slow vasogenic waves (SLOW). Results ICP was higher in LIAS than iNPH patients (9.3 ± 3.0 mmHg versus 5.4 ± 4.2 mmHg, p = 0.001). AMP and MWA were higher in iNPH versus LIAS (2.36 ± 0.91 mmHg versus 1.81 ± 0.59 mmHg for AMP, p = 0.012; 6.0 ± 2.0 mmHg versus 4.9 ± 1.2 mmHg for MWA, p = 0.049). RAP and SLOW indicated impaired reserve capacity and compliance in both diseases, but did not differ between groups. INPH patients were older than LIAS patients (77 ± 6 years versus 54 ± 14 years, p < 0.001). Conclusions ICP is higher in LIAS than in iNPH patients, likely due to the chronically obstructed CSF flow through the aqueduct, but still in a range considered normal. Interestingly, AMP/MWA was higher in iNPH patients, suggesting a possible role of high ICP pulse pressure amplitudes in iNPH pathophysiology. Cerebrospinal reserve capacity and intracranial compliance is impaired in both groups and the pressure-volume relationship might be shifted towards lower ICP values in iNPH. The physiological influence of age on ICP and AMP/MWA requires further research.

Identification of the TTC26 Splice Variant in a Novel Complex Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations

Ciliopathies constitute heterogeneous disorders that result from mutations in ciliary proteins. These proteins play an important role in the development of organs, physiology, and signaling pathways, and sequence variations in the genes encoding these proteins are associated with multisystem disorders. In this study, we describe a severe ciliopathy disorder that segregates in an autosomal recessive manner in a nonconsanguineous Saudi family. The proband exhibited features such as cholestasis, cystic dilatation of intrahepatic biliary ducts, diabetes insipidus, dysmorphic facial features, optic atrophy, pituitary hypoplasia, hydrocephalus, aqueductal stenosis, hyperextensible knee joints, bilateral knee dislocation, polydactyly, and syndactyly. Whole-genome sequencing and Sanger sequencing revealed a homozygous splice site variant (c.4–1G&#x3e;C; NM_024926.3) in the tetratricopeptide repeat domain 26 (<i>TTC26</i>) gene located in chromosome 7q34, which cosegregated perfectly with the disease phenotype. qRT-PCR revealed a substantial decrease in the expression of the <i>TTC26</i> gene as compared to the normal control, suggesting the pathogenicity of the identified variant. This report further strengthens the evidence that homozygous variants in the <i>TTC26</i> gene cause severe ciliopathies with diverse phenotypes. We named this newly characterized condition as BRENS syndrome, which stands for biliary, renal, neurological, and skeletal features.