Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder.

PURPOSE: SLC4A10 encodes a plasma membrane-bound transporter, which mediates Na+-dependent HCO3- import, thus mediating net acid extrusion. Slc4a10 knockout mice show collapsed brain ventricles, an increased seizure threshold, mild behavioral abnormalities, impaired vision, and deafness. METHODS: Utilizing exome/genome sequencing in families with undiagnosed neurodevelopmental disorders and international data sharing, 11 patients from 6 independent families with biallelic variants in SLC4A10 were identified. Clinico-radiological and dysmorphology assessments were conducted. A minigene assay, localization studies, intracellular pH recordings, and protein modeling were performed to study the possible functional consequences of the variant alleles. RESULTS: The families harbor 8 segregating ultra-rare biallelic SLC4A10 variants (7 missense and 1 splicing). Phenotypically, patients present with global developmental delay/intellectual disability and central hypotonia, accompanied by variable speech delay, microcephaly, cerebellar ataxia, facial dysmorphism, and infrequently, epilepsy. Neuroimaging features range from some non-specific to distinct neuroradiological findings, including slit ventricles and a peculiar form of bilateral curvilinear nodular heterotopia. In silico analyses showed 6 of 7 missense variants affect evolutionarily conserved residues. Functional analyses supported the pathogenicity of 4 of 7 missense variants. CONCLUSION: We provide evidence that pathogenic biallelic SLC4A10 variants can lead to neurodevelopmental disorders characterized by variable abnormalities of the central nervous system, including altered brain ventricles, thus resembling several features observed in knockout mice.

Trapped Fourth Ventricle: Pathophysiology, History and Treatment Strategies.

Trapped fourth ventricle is a clinic-radiological entity characterised by progressive neurological symptoms due to enlargement and dilatation of fourth ventricle secondary to obstruction to its outflow. There are several causative mechanisms for the development of trapped fourth ventricle, including previous haemorrhage, infection or inflammatory processes. However, this condition is most commonly observed in ex preterm paediatric patients shunted for a post-haemorrhagic or post-infective hydrocephalus. Until the introduction of endoscopic aqueductoplasty and stent placement, treatment of trapped fourth ventricle was associated with high rates of reoperation and complications resulting in morbidity. With the advent of new endoscopic techniques, supratentorial and infratentorial approaches for aqueductoplasty and stent insertion have revolutionised the treatment of trapped fourth ventricle. Fourth ventricular fenestration and direct shunting remain viable options in cases where aqueduct anatomy and length of obstruction is not surgically favourable for endoscopic approaches. In this book chapter, we explore the background, historical developments,$ and surgical treatment strategies in the management of this challenging condition.

Conservative and operative management of iatrogenic craniocerebral disproportion-a case-based review.

INTRODUCTION: Craniocerebral disproportion (CCD) can occur as a sequela after shunting in early infancy. It can be understood as a disorder closely related to slit ventricle syndrome and chronic overdrainage syndrome. Here, we present two exemplary cases and summarize the pathophysiological, diagnostic, and therapeutic approaches to CCD. CLINICAL PRESENTATION: Two premature babies underwent shunting for posthemorrhagic hydrocephalus and presented in later childhood with recurrent episodes of symptomatic raised intracranial pressure (ICP) at 2 and 8 years of age, respectively. DIAGNOSIS AND MANAGEMENT: Both patients had unchanged ventricular size on cranial imaging and fulfilled the clinical diagnostic criteria of CCD. After confirming shunt patency, ICP monitoring was performed to diagnose intermittent intracranial hypertension. Different treatment pathways were pursued: While readjustment of a programmable shunt valve was sufficient to alleviate the raised ICP in the first case, a cranial expansion surgery was necessary in the second case. OUTCOME AND CONCLUSIONS: Both children were treated successfully after thorough assessment and careful choice of treatment approaches. This review provides detailed insight into CCD and highlights the importance of individual and critical decision-making in these complex patients.

Shunt Testing In Vivo: Observational Study of Problems with Ventricular Catheter.

Most shunt obstructions happen at the inlet of the ventricular catheter. Three hundred six infusion studies from 2007 to 2011 were classified as having a typical pattern of either proximal occlusion or patency. We describe different patterns of shunt ventricular obstruction.Solid block: Cerebrospinal fluid (CSF) aspiration was impossible. Baseline pressure was without pulse waveform (respiratory waveform may be visible). A quick increase of pressure to a level compatible with the shunt's setting was recorded in response to infusion. Distal occlusion of the shunt via transcutaneous compression resulted in a rapid increase in pressure to levels above 50 mmHg. This pattern was attributed to a solid ventricular block.Slit ventricles: At baseline, a pattern similar to that of the solid block was observed. After compression, the pressure increases, the pulse waveform appears, and the intracranial pressure is often stabilized at 25-40 mmHg. It is probable that previously slit ventricles were opened during the test.Partial block: In a partial block of the ventricular catheter by an in-growing choroid plexus, the pulse waveform at baseline was observed and CSF aspiration was possible. During infusion, the pressure increased, but the pulse amplitude disappeared. During the increase in the pressure in the shunt prechamber, the connection with the ventricles is disturbed by repositioning of the plexus.Infusion study via the shunt prechamber is able to visualize ventricular obstruction of the hydrocephalus shunt.

Cerebrospinal Fluid Diversion from the Cisterna Magna in Patients with Idiopathic Intracranial Hypertension and Slit Ventricles: Long-Term Effectiveness, Revision Rates, and Clinical Outcomes.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) is a cerebrospinal fluid (CSF) disorder defect that is frequently treated with CSF shunts. Shunts utilizing the cisterna magna as a proximal reservoir have been described in literature; however, long-term outcomes are unknown. The present study aims to describe the long-term effectiveness, revision rates, and clinical outcomes of this shunt in 14 patients with IIH and slit ventricles. METHODS: A single-center retrospective review of 14 IIH patients treated by cisterna magna shunts was performed. Shunt histories, including revision rate and time until first shunt failure for ventricular, lumbar, and cisterna magna shunts were recorded. "Revision rate" was calculated as the total number of shunt revisions over years of total shunt placement. The average follow-up time was 12.08 years. RESULTS: The mean age at first cisterna magna shunt placement was 18.1 years (6.6-43.3 years) and all patients had radiological evidence of slit ventricles. Cisterna magna shunts improved or resolved clinical symptoms for all 14 patients and had a lower rate of revisions (0.42 revision/year) compared to ventricular (0.72 revision/year) and lumbar (1.30 revision/year) shunts. Of the 11 patients still requiring CSF diversion at the end of the study, eight had functioning shunts that utilized the cisterna magna. CONCLUSIONS: The cisterna magna shunt may be a suitable option for patients with IIH and slit ventricles. Further study is needed to understand the clinical utility of this shunt for the population in which it is indicated.

Intraoperative ultrasound-guided ventricular cannulation in patients with normal-sized ventricles.

INTRODUCTION: Many pathologies require normal-sized ventricle cannulation, which may be technically challenging even with neuronavigation guidance. This study presents a series of ventricular cannulation of normal-sized ventricles using intraoperative ultrasound (iUS) guidance and the outcomes of patients treated by this technique, for the first time. METHODS: The study included patients who underwent ultrasound-guided ventricular cannulation of normal-sized ventricles (either ventriculoperitoneal (VP) shunting or Ommaya reservoir) between January 2020 and June 2022. All patients underwent iUS-guided ventricular cannulation from the right Kocher's point. The inclusion criteria for normal-sized ventricles were as follows: (1) Evans index <30%, and (2) widest third ventricle diameter <6mm. Medical records and pre-, intra- and post-operative imaging were retrospectively analyzed. RESULTS: Nine of the 18 included patients underwent VP shunt placement; 6 had idiopathic intracranial hypertension (IIH), 2 had resistant cerebrospinal fluid fistula following posterior fossa surgery, and 1 had iatrogenic intracranial pressure elevation following foramen magnum decompression. Nine patients underwent Ommaya reservoir implantation, 6 of whom had breast carcinoma and leptomeningeal metastases and 3 hematologic disease and leptomeningeal infiltration. All catheter tip positions were achieved in a single attempt, and none were placed suboptimally. Mean follow-up was 10 months. One IIH patient (5.5%) had early shunt infection which necessitated shunt removal. CONCLUSION: iUS is a simple and safe method for accurate cannulation of normal-sized ventricles. It provides an effective real-time guidance option for challenging punctures.

Robot-guided Ventriculoperitoneal Shunt in Slit-like Ventricles.

BACKGROUND: Ventriculoperitoneal shunt (VPS) is the most common procedure used in the management of hydrocephalus regardless of the etiology. The standard free-hand technique is used for the placement of VPS in patients with enlarged ventricles. In patients with very small ventricles, CSF access through ventriculostomy becomes challenging and free-hand technique may be associated with high failure rates. In these situations, stereotactic-guided VPS becomes very useful. OBJECTIVE: To validate and describe the technique of robotic-guided VPS in cases with very small ventricles. METHODS: Three patients underwent VPS with robotic guidance between 2016 and 2019. One patient with a diagnosis of occipital meningocele, who later developed recalcitrant CSF leak from the operative site, and two other patients were diagnosed with idiopathic intracranial hypertension (IIH). Plain CT brain with 1-mm slice thickness acquired prior to the surgery was uploaded into the ROSA machine (Zimmer Biomet Warsaw, Indiana). The trajectory for the VPS is created on the robotic software presurgery. The patient is placed in the supine position with head turned to the side contralateral to VPS insertion and fixed with Mayfield clamp. Registration of the patient is done with the robot. The placement of the VPS is commenced with the robotic arm in the predetermined trajectory. RESULTS: Ventricle was hit in a single attempt in all the cases. CSF leak stopped in the case with meningocele; headache, and visual acuity improved in both the cases of IIH. CONCLUSION: Robotic-guidance provides a safe and accurate method of VPS placement even in the presence of slit-like ventricles.