Impact of standardized care guidelines featuring next-day discharge on outcome, healthcare consumption, and patient healthcare experience in patients with idiopathic normal pressure hydrocephalus receiving ventriculoperitoneal shunts.

OBJECTIVE: The aim of this study was to evaluate the effect of standardized care guidelines featuring next-day discharge on hospital length of stay (LOS), outcomes, patient experience, and healthcare consumption in patients receiving ventriculoperitoneal shunts (VPSs) for idiopathic normal pressure hydrocephalus (iNPH). METHODS: This single-center population-based observational cohort study included 271 adult iNPH patients who underwent VPS surgery at Karolinska University Hospital. Groups were compared before and after the implementation of new standardized discharge guidelines. The primary outcome was the hospital LOS. Secondary outcomes included postoperative complications, patient experience, and frequency of unscheduled outpatient follow-up appointments. RESULTS: A total of 121 patients were treated with variable hospitalization periods. One hundred fifty patients were managed under the new guidelines stipulating next-day discharge. There was no significant difference in positive surgical outcome (66% vs 71%, p = 0.372) or rates of complication (p ≥ 0.066) between groups. The standardized guidelines group had a significantly shorter period of inpatient hospitalization (1 vs 2 days, p < 0.001) and demonstrated lower levels of unscheduled outpatient healthcare consumption (p < 0.001) while maintaining levels of positive patient experience (p = 0.828). CONCLUSIONS: Standardized discharge guidelines featuring next-day discharge are safe for iNPH patients undergoing VPS surgery, maintain the quality of the patient experience, and are an effective method for mitigating healthcare consumption in an expanding patient group.

Evaluation of Miethke M.scio Device Implantation for Intracranial Pressure Monitoring in Patients with Cerebrospinal Fluid Disorders.

BACKGROUND: Patients with complex shunt-related problems and varying diagnoses of cerebrospinal fluid (CSF) disturbance can present with headache and clinical symptoms that may be difficult to relate to underdrainage or overdrainage. Telemetric intracranial pressure (ICP) monitoring may assist in evaluating individual patients and assessing shunt function and adjustment. We report a case series of patients receiving a Miethke M.scio sensor. METHODS: Between June 2016 and August 2021, 14 patients older than 18 years with different diagnoses underwent ventriculoperitoneal shunt surgery and received a Miethke M.scio sensor. RESULTS: Patients had idiopathic intracranial hypertension (n = 3), obstructive hydrocephalus caused by tumors (n = 4), and malformations (n = 5). Headaches (71%) and visual impairment (50%) were the most common symptoms before surgery and 65% of the symptoms were improved after surgery. In total, 25 measurements were made and 11 of these led to changes in the shunt settings. Postoperative measurements were taken in 8 patients and the most common indication of ICP measurement was headache and/or control of the shunt settings. CONCLUSIONS: The Miethke M.scio is a safe and valuable device to use in shunt-treated patients, in particular those expected to need assessment of ICP monitoring postoperatively. Repeated ICP measurements can also assist in personalized adjustment of the shunt setting to optimize CSF flow in this diverse patient group. Future studies should include a standardized protocol with ICP measurements correlated to the symptoms and cause of CSF disturbances to provide better understanding of the dynamics of the ICP in each patient.

Preoperative Prognostic Index for Patients with Brain Metastases-A Population-Based Multi-Centre Study.

BACKGROUND: Brain metastases (BM) are common in cancer patients and are associated with high morbidity and mortality. Surgery is an option, but the optimal selection of patients for surgery is challenging and controversial. Current prognostication tools are not ideal for preoperative prognostication. By using a reference population (derivation data set) and two external populations (validation data set) of patients who underwent surgery for BM, we aimed to create and validate a preoperative prognostic index. METHODS: The derivation data set consists of 590 patients who underwent surgery for BM (2011-2018) at Oslo University Hospital. We identified variables associated with survival and created a preoperative prognostic index with four prognostic groups, which was validated on patients who underwent surgery for BM at Karolinska University Hospital and St. Olavs University Hospital during the same time period. To reduce over-fitting, we adjusted the index in accordance with our findings. RESULTS: 438 patients were included in the validation data set. The preoperative prognostic index correctly divided patients into four true prognostic groups. The two prognostic groups with the poorest survival outcomes overlapped, and these were merged to create the adjusted preoperative prognostic index. CONCLUSION: We created a prognostic index for patients with BM that predicts overall survival preoperatively. This index might be valuable in supporting informed choice when considering surgery for BM.

Gait, falls, cognitive function, and health-related quality of life after shunt-treated idiopathic normal pressure hydrocephalus-a single-center study.

BACKGROUND: Normal pressure hydrocephalus (NPH) is a neurological disorder, characterized by gait- and balance disturbance, cognitive deterioration, and urinary incontinence, combined with ventricular enlargement. Gait ability, falls, cognitive status, and health-related quality of life pre and post surgery have not previously been studied at Karolinska University Hospital. METHODS: One hundred and eighteen patients with iNPH that underwent shunt surgery at Karolinska University Hospital during the years from 2016 to 2018 were included. Results of walking tests, test for cognitive function, and self-estimated health-related quality of life, before and 3 months after surgery, were collected retrospectively as a single-center study. RESULTS: Walking ability, cognitive function, and health-related quality of life significantly increased 3 months after shunt surgery. A positive significant correlation was seen between a higher self-estimated quality of life and walking ability. CONCLUSIONS: Patients with suspected iNPH treated with shunt surgery at Karolinska University Hospital improved their walking ability and cognitive functioning 3 months after shunt surgery. A positive significant correlation was seen between a higher self-estimated quality of life and walking ability but not with increased cognitive function. We then concluded that the selection of patients for shunting maintained a high standard.

The demography of idiopathic normal pressure hydrocephalus: data on 3000 consecutive, surgically treated patients and a systematic review of the literature.

OBJECTIVE: The objective of this study was to describe the demographic characteristics of patients with idiopathic normal pressure hydrocephalus (iNPH) through an analysis of 3000 consecutive, surgically treated Swedish patients and a systematic review of the literature. METHODS: Data on age, sex, comorbidities, diagnostic delay, initial symptoms, and severity of symptoms at diagnosis were extracted from the Swedish Hydrocephalus Quality Registry. In addition, a systematic PRISMA-based review of the literature published from database inception until August 2019 was performed using the PubMed, Cochrane, and Scopus databases on the basis of two concepts: normal pressure hydrocephalus and demography and their association with related terms. Of 1020 unique articles, 16 were eligible for study inclusion and were assessed for quality using the Newcastle-Ottawa Scale. Mean and weighted mean values were calculated. RESULTS: The mean patient age at the time of surgery was 74.4 years, 79% of patients were in their 70s, and 60% of the patients were men. Almost 50% of the patients had symptoms from four main domains (i.e., balance, gait, cognition, and urinary dysfunction) at disease onset. Patients aged < 60 years (2%) reported more headaches and fewer balance problems than those aged ≥ 60. Women were more impaired in function than men at the time of diagnosis. Dementia (Mini-Mental State Examination score < 25) was found in 47% of the patients. Men had more diabetes, heart disease, hypertension, and stroke than women, and comorbidity correlated with increased impairment. The incidence of surgery for iNPH was 20%-40% of the disease incidence according to survey and operation-based studies. CONCLUSIONS: Most iNPH patients undergo surgery in their 70s. Those aged < 60 years show slightly different symptomatology and probably present with a specific disease entity, indicating that the lower age limit for iNPH should be 60 years. iNPH patients have severe impairment preceded by a long diagnostic delay. Even though the included study designs differed, the systematic review showed that the disorder has a very low treatment incidence. The importance of diagnosing and treating iNPH is further emphasized by the fact that iNPH may account for a considerable part of all cases of dementia.

Distribution and characterization of progenitor cells within the human filum terminale.

BACKGROUND: Filum terminale (FT) is a structure that is intimately associated with conus medullaris, the most caudal part of the spinal cord. It is well documented that certain regions of the adult human central nervous system contains undifferentiated, progenitor cells or multipotent precursors. The primary objective of this study was to describe the distribution and progenitor features of this cell population in humans, and to confirm their ability to differentiate within the neuroectodermal lineage. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that neural stem/progenitor cells are present in FT obtained from patients treated for tethered cord. When human or rat FT-derived cells were cultured in defined medium, they proliferated and formed neurospheres in 13 out of 21 individuals. Cells expressing Sox2 and Musashi-1 were found to outline the central canal, and also to be distributed in islets throughout the whole FT. Following plating, the cells developed antigen profiles characteristic of astrocytes (GFAP) and neurons (ß-III-tubulin). Addition of PDGF-BB directed the cells towards a neuronal fate. Moreover, the cells obtained from young donors shows higher capacity for proliferation and are easier to expand than cells derived from older donors. CONCLUSION/SIGNIFICANCE: The identification of bona fide neural progenitor cells in FT suggests a possible role for progenitor cells in this extension of conus medullaris and may provide an additional source of such cells for possible therapeutic purposes. Filum terminale, human, progenitor cells, neuron, astrocytes, spinal cord.

TLR activation induces TNF-alpha production from adult neural stem/progenitor cells.

Adult neural stem cells (NSCs) are believed to facilitate CNS repair and tissue regeneration. However, it is not yet clear how these cells are influenced when the cellular environment is modified during neurotrauma or neuroinflammatory conditions. In this study, we determine how different proinflammatory cytokines modulate the expression of TLR2 and TLR4 in NSCs and how these cells respond to TLR2 and TLR4 agonists. Primary cultures of neural stem/progenitor cells isolated from the subventricular zone of brains from adult Dark Agouti rats were exposed to 1) supernatants from activated macrophages; 2) proinflammatory cytokines IFN-gamma, TNF-alpha, or both; and 3) agonists for TLR2 and TLR4. Both TLR2 and TLR4 were expressed during basal conditions and their mRNA levels were further increased following cytokine exposure. TLR4 was up-regulated by IFN-gamma and this effect was reversed by TNF-alpha. TLR2 expression was increased by supernatants from activated macrophages and by TNF-alpha, which synergized with IFN-gamma. TLR agonists induced the expression of TNF-alpha mRNA. Importantly, TNF-alpha could be translated into protein and released into the supernatants where it was quantified by cytokine ELISA. In conclusion, we demonstrate that NSCs constitutively express TLR2 and TLR4 and that their expression is increased as a consequence of exposure to proinflammatory mediators. Additionally, activation of these receptors can induce production of proinflammatory cytokines. These findings suggest that NSCs may be primed to participate in cytokine production during neuroinflammatory or traumatic conditions.