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Alzheimer's Research & Therapy Sep 2021Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid...
BACKGROUNDS
Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies.
OBJECTIVES
We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer's disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood-derived MSCs (hUCB-MSCs).
METHODS
We recruited nine mild-to-moderate Alzheimer's disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 10 cells/2 mL), and six patients received a high dose (3.0 × 10 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study.
RESULTS
After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed.
CONCLUSIONS
Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017.
Topics: Alzheimer Disease; Animals; Fetal Blood; Follow-Up Studies; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 34521461
DOI: 10.1186/s13195-021-00897-2 -
Cureus Apr 2020Ommaya reservoir insertion is an elective neurosurgical procedure to deliver repeated intraventricular therapy, but placement can be complicated by malposition of the...
Ommaya reservoir insertion is an elective neurosurgical procedure to deliver repeated intraventricular therapy, but placement can be complicated by malposition of the catheter, clogging, infection or poor postoperative cosmesis. Here, we describe the technique used by the senior author for accurate placement including preassembly of the reservoir and catheter, and recessing of the reservoir so that others may consider the technique for their practice. Results in a consecutive series of 27 Ommaya placements were reviewed. Catheter tip placement accuracy, complications and surgical times were reported. Indications were leptomeningeal cancer or infection. Postoperative imaging showed the catheter tip was located in the frontal horn (96%) or body (4%) of the ipsilateral lateral ventricle. The median surgical time was 36 minutes (range 17-63 minutes). There were no parenchymal or subarachnoid hemorrhages. Infections occurred in 7% (n=2) of cases, and both infections presented greater than 60 days postoperative. In conclusion, we have found that image guidance can optimize accuracy in placement, that preassembly of the reservoir and catheter may be used with a 25-gauge spinal needle stylet to minimize risk of clogging during placement, and that recessing of the reservoir produces the best aesthetic result.
PubMed: 32432009
DOI: 10.7759/cureus.7731 -
Cancer Control : Journal of the Moffitt... Jan 2017Advancements in cancer treatment have led to more cases of leptomeningeal disease, which requires a multimodal approach. (Review)
Review
BACKGROUND
Advancements in cancer treatment have led to more cases of leptomeningeal disease, which requires a multimodal approach.
METHODS
Treatment modalities are reviewed from a neurosurgical standpoint, focusing on intrathecal chemotherapy and shunting devices. Potential complications and how to avoid them are discussed.
RESULTS
The Ommaya reservoir and the chemoport are used for administering intrathecal chemotherapy. Use of ventriculo-lumbar perfusion can efficiently deliver chemotherapeutic agents and improve intracerebral pressure. Shunting systems, in conjunction with all of their variations, address the challenge of hydrocephalus in leptomeningeal carcinomatosis. Misplaced catheters, malfunction of the system, and shunt-related infections are known complications of treatment.
CONCLUSIONS
From an oncological perspective, the surgical treatment for leptomeningeal disease is limited; however, neurosurgery can be used to aid in the administration of chemotherapy and address the issue of hydrocephalus. Minimizing surgical complications is important in this sensitive patient population.
Topics: Humans; Meningeal Neoplasms; Prognosis
PubMed: 28178712
DOI: 10.1177/107327481702400107 -
World Neurosurgery Dec 2019Treatment of cystic craniopharyngiomas can be challenging and recurrences are frequent, even after total resection. In selected cases, less-aggressive surgery with the... (Review)
Review
OBJECTIVE
Treatment of cystic craniopharyngiomas can be challenging and recurrences are frequent, even after total resection. In selected cases, less-aggressive surgery with the sole drainage of the cyst reliefs symptoms caused by mass effect and represents a valid alternative option, notably in pediatric population. We herein analyze a series of adult cystic craniopharyngiomas, managed with Ommaya Reservoir implant, focusing on local tumor control and eventual complications.
METHODS
In total, 11 nonconsecutive adult cystic craniopharyngiomas (7 recurrent lesions) were treated with Ommaya Reservoir System (ORS), in 2 neurosurgical centers. ORS was placed in 9 cases using minimally invasive procedures: 6 burr-hole endoscopic insertion and 3 navigated electromagnetic placement; in the remaining 2 patients, the Ommaya reservoir was used as a shunt to prevent cyst recollection during a transcranial approach.
RESULTS
The main presenting symptoms were visual impairment (75%), cognitive and behavioral disorders (66.7%), hypopituitarism (38%), headache (30.8%), and hypothalamic obesity (8%). The median follow-up period was 41.4 months. In all patients, the visual function and intracranial hypertension improved after decompression. Local tumor control was accomplished in 8 patients (72.7%), without the need of adjuvant treatments. The endoscopic vision carried similar rates of tumor control than stereotaxy (75% vs. 66.7%).
CONCLUSIONS
In selected patients, tailored procedures are required to achieve long-term tumor control and as well limit surgery-related morbidity. ORS could represent a safe and effective treatment option for cystic craniopharyngiomas, providing also reduced surgical-related morbidity, especially in recurrent lesions and in patients not suitable for radical surgery.
Topics: Adolescent; Adult; Aged; Cognitive Dysfunction; Craniopharyngioma; Cysts; Drainage; Electromagnetic Fields; Female; Headache; Humans; Hypopituitarism; Intracranial Hypertension; Male; Mental Disorders; Middle Aged; Neuroendoscopy; Neurosurgical Procedures; Pituitary Neoplasms; Retrospective Studies; Stereotaxic Techniques; Vision Disorders; Young Adult
PubMed: 31400528
DOI: 10.1016/j.wneu.2019.07.217 -
Neurology India 2021Endoscopic third ventriculostomy (ETV) has become a proven modality for treating obstructive and selected cases of communicating hydrocephalus. (Review)
Review
BACKGROUND
Endoscopic third ventriculostomy (ETV) has become a proven modality for treating obstructive and selected cases of communicating hydrocephalus.
OBJECTIVE
This review aims to summarize the indications, preoperative workup, surgical technique, results, postoperative care, complications, advantages, and limitations of an ETV.
MATERIALS AND METHODS
A thorough review of PubMed and Google Scholar was performed. This review is based on the relevant articles and authors' experience.
RESULTS
ETV is indicated in obstructive hydrocephalus and selected cases of communicating hydrocephalus. Studying preoperative imaging is critical, and a detailed assessment of interthalamic adhesions, the thickness of floor, arteries or membranes below the third ventricle floor, and prepontine cistern width is essential. Blunt perforation in a thin floor, while bipolar cautery at low settings and water jet dissection are preferred in a thick floor. The appearance of stoma pulsations and intraoperative ventriculostomography reassure stoma and basal cistern patency. The intraoperative decision for shunt, external ventricular drainage, or Ommaya reservoir can be taken. Magnetic resonance ventriculography and cine phase-contrast magnetic resonance imaging can determine stoma patency. Good postoperative care with repeated cerebrospinal fluid drainage enhances outcomes in selected cases. Though the complications mostly occur in an early postoperative phase, delayed lethal ones may happen. Watching live surgeries, assisting expert surgeons, and practicing on cadavers and models can shorten the learning curve.
CONCLUSION
ETV is an excellent technique for managing obstructive and selected cases of communicating hydrocephalus. Good case selection, methodical technique, and proper training under experts are vital.
Topics: Cerebral Ventricles; Humans; Hydrocephalus; Magnetic Resonance Imaging; Third Ventricle; Ventriculostomy
PubMed: 35103009
DOI: 10.4103/0028-3886.332253 -
No Shinkei Geka. Neurological Surgery Nov 2022Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of...
Childhood hydrocephalus is a highly diverse disease caused by various factors, and most surgical treatments are performed during infancy. Despite the diversity of hydrocephalus pathologies, treatment options are limited. It is difficult for pediatric neurosurgeons to select and perform appropriate surgical procedures for neonates and infants. Treatment options for hydrocephalus are broadly divided into permanent and temporary. Permanent treatments include cerebrospinal fluid shunt and endoscopic third ventriculostomy; temporary treatment entails cerebrospinal fluid drainage using lumbar puncture and intermittent cerebrospinal fluid drainage with an Ommaya reservoir, ventricular drainage, and ventriculosubgaleal shunt. This article describes in detail Ommaya reservoir placement and ventricular drainage as representative procedures for temporarily treating hydrocephalus.
Topics: Infant, Newborn; Infant; Humans; Child; Cerebral Hemorrhage; Retrospective Studies; Hydrocephalus; Drainage; Cerebrospinal Fluid Leak
PubMed: 36426516
DOI: 10.11477/mf.1436204682 -
Child's Nervous System : ChNS :... Jun 2021Optic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3-5% of all pediatric brain tumors. They are most commonly... (Review)
Review
BACKGROUND
Optic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3-5% of all pediatric brain tumors. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumors results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other eloquent brain structures typically precludes complete resection or optimal radiation dosing without incurring significant neurological injury. There are various surgical interventions that can be performed in relation to these lesions including biopsy, cerebrospinal fluid diversion, and partial or radical resection, but their role is a source of debate. This study catalogues our surgical experience and patient outcomes in order to support decision-making in this challenging pathology.
METHODS
A retrospective review of all cases of OPGs treated in a single center from July 1990 to July 2020. Data was collected on patient demographics, radiographic findings, pathology, and management including surgical interventions. Outcome data included survival, visual function, endocrine, and hypothalamic dysfunction.
RESULTS
One hundred twenty-one patients with OPG were identified, and 50 of these patients underwent a total of 104 surgical procedures. These included biopsy (31), subtotal or gross total resection (20 operations in 17 patients), cyst drainage (17), Ommaya reservoir insertion (9), or cerebrospinal fluid diversion (27). During the study period, there was 6% overall mortality, 18% hypothalamic dysfunction, 20% endocrine dysfunction, and 42% had some cognitive dysfunction. At diagnosis 75% of patients had good or moderate visual function in at least one eye, and overall, this improved to 83% at the end of the study period. In comparison the worst eye had good or moderate visual function in 56%, and this reduced to 53%. Baseline and final visual function were poorer in patients who had a surgical resection, but improvements in vision were still found-particularly in the best eye.
DISCUSSION/CONCLUSION
OPG are debilitating childhood tumor that have lifelong consequences in terms of visual function and endocrinopathies/hypothalamic dysfunction; this can result in substantial patient morbidity. Decisions regarding management and the role of surgery in this condition are challenging and include cerebrospinal fluid diversion, biopsy, and in highly select cases cystic decompression or surgical resection. In this paper, we review our own experience, outcomes, and surgical philosophy.
Topics: Astrocytoma; Brain Neoplasms; Child; Humans; Neurofibromatosis 1; Neurosurgical Procedures; Optic Nerve Glioma; Retrospective Studies; Treatment Outcome
PubMed: 33532921
DOI: 10.1007/s00381-021-05060-8 -
Child's Nervous System : ChNS :... Aug 2023Diffuse midline brainstem gliomas have a poor prognosis and are generally not amenable to surgical resection. Occasionally, palliative surgical procedures can be... (Review)
Review
INTRODUCTION
Diffuse midline brainstem gliomas have a poor prognosis and are generally not amenable to surgical resection. Occasionally, palliative surgical procedures can be performed to improve the quality of life of these patients. We describe three patients with solid-cystic brainstem gliomas in whom an Ommaya reservoir catheter was placed to reduce mass effect.
OBJECTIVES
To describe the characteristics, indications for, and operative technique of Ommaya reservoir catheter placement in patients with solid-cystic diffuse midline glioma.
MATERIALS AND METHODS
A review was conducted of the medical records of pediatric patients with solid-cystic diffuse midline glioma H3 K27-altered, treated with an Ommaya reservoir at Hospital J.P. Garrahan between 2014 and 2021 together with a search of the literature.
RESULTS
Three cases of stereotaxic Ommaya placement in solid-cystic diffuse midline gliomas, H3 K27M-altered were identified. After the procedure, clinical improvement and reduction of the size of the tumor cyst size was achieved. No associated complications were seen. At the time of the study, one patient died, and the remaining two patients continued in follow-up at our hospital.
CONCLUSION
We believe that the placement of an intratumoral Ommaya reservoir catheter may be considered a therapeutic option to improve symptoms and quality of life of selected patients with solid-cystic diffuse midline glioma.
Topics: Humans; Child; Brain Neoplasms; Histones; Quality of Life; Mutation; Glioma; Brain Stem Neoplasms
PubMed: 37072561
DOI: 10.1007/s00381-023-05950-z -
Brain Pathology (Zurich, Switzerland) Nov 2016If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor... (Review)
Review
If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit not sufficient, condition to effectively target the disease. In order to analyze the current status of research on drug delivery to high grade gliomas (HGG-WHO grades III and IV), the most frequent and aggressive brain cancers, a literature search was conducted in PubMed using the terms: "drug delivery and brain tumor" over the publication year 2015. Currently explored drug delivery techniques for HGG include the convection and permeabilization-enhanced deliveries, drug-releasing depots and Ommaya reservoirs. The efficacy/safety ratio widely varies among these techniques and the success of current efforts to increase this ratio widely varies as well.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Convection; Drug Delivery Systems; Glioma; Humans
PubMed: 27488680
DOI: 10.1111/bpa.12423