Directed differentiation of human hindbrain neuroepithelial stem cells recapitulates cerebellar granule neurogenesis.

Cerebellar granule neurons (CGNs) are the most abundant neurons in the human brain. Dysregulation of their development underlies movement disorders and medulloblastomas. It is suspected that these disorders arise in progenitor states of the CGN lineage, for which human models are lacking. Here, we have differentiated human hindbrain neuroepithelial stem (hbNES) cells to CGNs in vitro using soluble growth factors, recapitulating key progenitor states in the lineage. We show that hbNES cells are not lineage committed and retain rhombomere 1 regional identity. Upon differentiation, hbNES cells transit through a rhombic lip (RL) progenitor state at day 7, demonstrating human specific sub-ventricular cell identities. This RL state is followed by an ATOH1+ CGN progenitor state at day 14. By the end of a 56-day differentiation procedure, we obtain functional neurons expressing CGN markers GABAARα6 and vGLUT2. We show that sonic hedgehog promotes GABAergic lineage specification and CGN progenitor proliferation. Our work presents a new model with which to study development and diseases of the CGN lineage in a human context.

Giant choroid plexus cysts with calvarial erosion: a case report and literature review.

Choroid plexus cysts rarely grow to be symptomatic. Few large choroid plexus cysts have been reported in the pediatric population. The authors report a 15-month-old boy with increased head circumference and a bony deformity in the left parietal region due to mass effect from a giant choroid plexus cyst. The child had a craniotomy for open resection of the cyst, and made an excellent recovery. The differential diagnosis for intraventricular cysts and the literature surrounding choroid plexus cysts are discussed.

Stopping CSF leaks at external ventricular drain exit sites: a technical note.

PURPOSE: Cerebrospinal fluid (CSF) leak is a major risk factor for external ventricular drain infection. Here, we present a surgical technique to reduce the possibility of CSF leak at the external ventricular drain (EVD) exit site in high-risk patients. METHODS: Vertical mattress sutures are placed circumferentially around the EVD catheter tract as it passes under the skin, so to close off the tract along which CSF may travel toward the exit site. RESULTS: Specific case examples are discussed where the introduction of this technique was found to be helpful in stopping exit-site CSF leak. CONCLUSION: In our experience, these surgical steps are useful adjuncts that should be considered in all high-risk patients undergoing EVD placement.

Frameless Stereotactic Biopsy of Brainstem Tumors Using the Stealth Autoguide: A Technical Note.

BACKGROUND AND OBJECTIVES: In the molecular era of neuro-oncology, it is increasingly necessary to obtain tissue for next-generation sequencing and methylome profile for prognosis and targeted oncological management. Brainstem tumors can be technically challenging to biopsy in the pediatric population. Frame-based and frameless techniques have previously been described and proven to be safe and efficacious in children. Recent cranial robotic guidance platforms have augmented the fluency of frameless stereotactic approaches, but the technical nuances of these procedures in children are not often discussed. We present a technical workflow for frameless stereotactic biopsy of brainstem tumors in children using the Medtronic Stealth Autoguide cranial robotic guidance platform and examine safety and efficacy of this surgical approach. METHODS: A minimally invasive, frameless, transcerebellar approach is described, including operative steps and workflow. We assessed operative times, diagnostic accuracy and yield, and complication rates. RESULTS: Five patients underwent biopsy with the technique described. The youngest patient in our series was of 2 years. The intended target was achieved on postoperative imaging in all cases, and diagnostic tissue was obtained in all 5 patients. One patient had a clinically insignificant hemorrhage. CONCLUSION: Frameless stereotactic biopsy of the brainstem can be performed safely, efficiently, and accurately using the Medtronic Stealth Autoguide robotic platform in children as young as 2 years.

The development of ring-shaped contrast enhancement in a case of cerebellar dysembryoplastic neuroepithelial tumor: case report.

OBJECTIVE: Dysembryoplastic neuroepithelial tumor (DNT) occurs rarely in the cerebellum. We describe a rare case of cerebellar DNT that developed contrast enhancement after long-term observation and discuss the underlying mechanism and clinical relevance of this unusual phenomenon. CLINICAL PRESENTATION: A 34-year-old woman with known cystic cerebellar lesions presented with increased frequency of vertigo and new onset of truncal ataxia. Magnetic resonance imaging revealed new contrast enhancement in the dominant cystic lesion of the cerebellar vermis without any change in size and shape or evidence of edema. INTERVENTION: The lesions were resected under magnetic resonance imaging guidance. Histological assessment revealed populations of small, round cells in a microcystic background containing "floating" neurons, diagnostic of DNT. Microvascular proliferation and pigmented neurons were also present. CONCLUSION: This is the first report of the development of contrast enhancement in a previously nonenhancing case of cerebellar DNT. The acquisition of ring-shaped contrast enhancement may be associated with microvascular proliferation, but otherwise no evidence of malignant progression. In addition, this case presents the novel pathological finding of pigmented neurons in DNT.