Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming ...of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
Interstitial photodynamic therapy (iPDT) with 5-aminolevulinic acid (ALA) is a possible alternative treatment for malignant brain tumors. Further evaluation is, however, required before it can be ...clinically applied. Computational simulation of the photophysical process in ALA-iPDT can offer a quantitative tool for understanding treatment outcomes, which depend on various variables related to clinical treatment conditions. We propose a clinical simulation method of ALA-iPDT for malignant brain tumors using a singlet oxygen (O12) model and O12 threshold to induce cell death. In this method, the amount of O12 generated is calculated using a photosensitizer photobleaching coefficient and O12 quantum yield, which have been measured in several previous studies. Results of the simulation using clinical magnetic resonance imaging data show the need to specify the insertion positions of cylindrical light diffusers and the level of light fluence. Detailed analysis with a numerical brain tumor model demonstrates that ALA-iPDT treatment outcomes depend on combinations of photobleaching and threshold values. These results indicate that individual medical procedures, including pretreatment planning and treatment monitoring, will greatly benefit from simulation of ALA-iPDT outcomes.
•Balance disturbance in idiopathic normal pressure hydrocephalus (iNPH) patients may relate to saccular dysfunction.•Cervical vestibular evoked myogenic potential tuning shift may be a determining ...factor in iNPH diagnosis and treatment.•Excessive cerebrospinal fluid accumulation and slightly elevated intracranial pressure in the iNPH may propagate to the inner ear.
The purpose of this study was to investigate the effects of excessive cerebrospinal fluid (CSF) retention on the peripheral vestibular function and the inner ear fluid in patients with idiopathic normal pressure hydrocephalus (iNPH).
In 25 patients with iNPH (14 females, age 65–88 years), cervical vestibular evoked myogenic potential (cVEMP) was measured before the spinal tap test. The asymmetry ratios (ARs) and tuning properties in 500 Hz and 1,000 Hz short-tone burst stimuli of cVEMP were evaluated. Furthermore, cVEMP was measured in an age-matched control group of 12 non-iNPH patients.
Seven (28%) iNPH patients exhibited a cVEMP asymmetry (AR > 33%). cVEMP tuning was significantly shifted to a higher frequency in the iNPH group than in the age-matched control group.
One-fourth of patients with iNPH had obvious saccular dysfunction. A high rate of a shift in cVEMP tuning in the iNPH group indicated that excessive CSF accumulation propagated to the endolymph and perilymph.
Saccular dysfunction might be one of the possible causes of imbalance in iNPH, and the shift in cVEMP tuning may be a determining factor in the diagnosis and treatment strategy.
Primary brain tumors occur in around 250,000 people per year globally. Survival rates in primary brain tumors depend on the type of tumor, patient's age, the extent of surgical tumor removal, and ...other factors. Photodynamic diagnosis (PDD) is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma and meningiomas, whereas clinical application of photodynamic therapy (PDT) to brain tumor therapy has just recently started. Both PDD and PDT are achieved by a photon-induced physicochemical reaction, which is induced by the excitation of porphyrins exposed to light. In fluorescence-guided gross-total resection, PDD can be achieved by the administration of 5-aminolevulinic acid (5-ALA) as the precursor of protoporphyrin IX (PpIX). Exogenously administered ALA induces biosynthesis and accumulation of PpIX, a natural photosensitizer, in cancer cells. However, ATP-binding cassette transporter ABCG2 plays a critical role in regulating the cellular accumulation of porphyrins in cancer cells and thereby its expression and function can affect the efficacy of PDD and PDT. In response to the photoreaction of porphyrins leading to oxidative stress, the nuclear factor erythroid-derived 2-related transcription factor can transcriptionally upregulate ABCG2, which may reduce the efficacy of PDD and PDT. On the other hand, certain protein kinase inhibitors potentially enhance the efficacy of PDD and PDT by blocking ABCG2-mediated porphyrin efflux from cancer cells. In this context, it is of great interest to develop ABCG2 inhibitors that can be applied to PDD or PDT for the therapy of brain tumor and other tumors.
Objectives
To clarify a characteristic of dynamic stability during gait in idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD), and to explore the association between dynamic ...stability and disease severity in each disease.
Materials and Methods
The 5‐m gait of 36 iNPH (precerebrospinal fluid drainage), 20 PD (medicated state), and 25 healthy controls (HC) were evaluated using three‐dimensional motion analysis. Ambulatory dynamic stability was defined as the ability to maintain the extrapolated center of mass within the base of support at heel contact, with the distance between the two referred to as the margin of stability (MOS).
Results
Anteroposterior direction (AP) MOS was significantly larger in the iNPH and PD groups than in the HC group; no significant difference was found between the iNPH and PD groups. Mediolateral direction (ML) MOS was significantly larger in the iNPH and PD groups than in the HC group and significantly larger in the iNPH group than in the PD group. In the iNPH group, the disease severity was positively correlated with only ML MOS. In the PD group, the disease severity was positively correlated with the AP MOS and ML MOS.
Conclusions
Dynamic stability in iNPH increases in AP and ML, and it may be associated with not only iNPH‐associated gait disturbance but also with a voluntarily cautious gait strategy. Dynamic stability in PD only increased in AP, and this may be associated with PD symptoms. These findings will help physicians understand the difference in pathological gait including dynamic stability between patients with iNPH and PD.
Cranial sutures are narrow mesenchymal tissues that connect skull bones to each other. Given that they serve as growth centers in the skull, these undifferentiated tissues play crucial roles in skull ...development. Cranial sutures are also of clinical importance, because the premature fusion of skull bones results in a pathological condition called craniosynostosis. In newborns, skull sutures are wide and straight; during adolescence, they become thinner and start winding to form an interdigitating pattern. From a functional aspect, as the degree of interdigitation becomes larger, the strength of the connection between bones increases. However, the mechanisms underlying the maintenance of mesenchymal narrow bands or formation of interdigitation remain poorly understood. In the present study, we presented a new mathematical model that can reproduce the suture width maintenance and interdigitation formation. We can predict the width of the mesenchyme bands and wavelengths of suture interdigitations from the model.
•We formulate simplest possible mathematical model for skull suture interdigitation.•The model reproduces all the experimentally observed patterns.•Numerical simulation and mathematical analysis made easy by the simplicity of the model.
We identified a new type of shunt malfunction (SM) in patients with normal pressure hydrocephalus (NPH). It is induced by weight change and can be treated with valve readjustment. There were two ...types of SM as follows: Underdrainage induced by the weight gain and overdrainage induced by the weight loss. This study aims to elucidate this mechanism by assessing the shunt pressure environment.
The total pressure environment of the shunt system was prospectively studied in patients with shunted NPH at Osaka Medical College Hospital from 1999 to 2005. We measured the pressure environment during the initial pressure setting of the valve by the intracranial pressure (ICP) guide, after setting the valve, and when SM was suspected. We evaluated ICP, intra-abdominal pressure (IAP), and hydrostatic and perfusion pressures of the shunt system in the sitting and supine positions. The target ICP for valve setting was empirically set at the range from -8 to -13 mm Hg in the sitting position, referring to the external auditory meatus. During the study period, we identified five cases of SM induced by weight change and assessed the changes in the pressure environment across pre-SM, SM, and post-SM.
In four cases of underdrainage, gait disturbance worsened with an average weight gain of 6.8 ± 1.2 kg. With weight gain, IAP and ICP increased by 8.8 ± 1.6 and 4.8 ± 1.0 mm Hg, respectively. Consequently, ICP increased to -6.5 ± 1.9 mm Hg. One overdrainage patient developed an asymptomatic chronic subdural hematoma (CSDH) with a weight loss of 10 kg. With the weight loss, both IAP and ICP decreased by 5 mm Hg, and concomitantly, ICP decreased to -18 mm Hg. In all patients, the valve readjustment restored their ICP to the target pressure. After the valve readjustment, the gait disturbance improved immediately, and the CSDH disappeared after 1 month.
In patients with shunts, the weight change was linked to ICP
IAP. Due to the weight change, the underdrainage occurred when ICP was above the target pressure, and the overdrainage occurred when ICP was below it. We named this SM as the weight and abdominal pressure-induced shunt trouble. The patients with SM along with weight changes should be the first to be tried for the valve readjustment.
•iNPH-associated gait and balance disturbances can increase the risk of falling.•The factors influencing falls in patients with iNPH remain unclear.•Advanced age and gait-balance instability ...increased the risk of falling.•Our findings may help identify patients who are at high risk of falling.•This will allow the implementation of suitable prevention strategies.
The factors influencing falls in idiopathic normal pressure hydrocephalus (iNPH) remain unclear, although iNPH-associated gait and balance disturbances can lead to an increased risk of falls. This study aimed to investigate the associations among fall status, gait variability, balance function in iNPH, and to identify fall-related factors in iNPH.
Sixty-three patients with iNPH with a positive cerebrospinal fluid tap test result according to the iNPH diagnosis criteria participated in this prospective cross-sectional study. Patients were assessed using the 10-meter walk test (10MWT), the Functional Gait Assessment (FGA), the Berg Balance Scale (BBS), and the isometric quadriceps strength (QS). We also investigated each patient’s history of falls in the past 6 months. Gait variability was measured using a triaxial accelerometer attached to the patient’s torso at the L3 vertebra level during the 10MWT.
Fall status correlated significantly with gait variability (measured as the coefficient of variation; CV) in step time and movement trajectory amplitude (i.e., center of mass movement) in the medial/lateral (ML) and vertical (VT) directions, with balance function as assessed by FGA and BBS scores. In contrast, QS was not correlated with fall status. The independent variables associated with the risk of falling were step time CV, FGA score, and age.
The factors associated with the risk of falling in iNPH were aging and gait-balance instability, particularly temporal gait variability and dynamic balance dysfunction. Our results may enable physicians to identify the patients with iNPH who are at risk of falling and implement suitable prevention strategies.
The objective of this study was to verify that spine surgery for late-stage elderly (LSE) (age 65–74 years) is as safe as that for early-stage elderly (ESE) (age 65–74 years).
This retrospective ...multicenter study included elderly patients aged ≥65 years who underwent spine surgery between 2018 and 2021. The medical information for individual patients was obtained from medical records. Activities of daily living (ADL) were estimated using a 5-grade scale based on the Eastern Cooperative Oncology Group performance status. Good outcome was defined as ADL grade 0 or 1 at discharge; poor outcome was defined as ADL grade 2 to 4 at discharge. The postoperative complications were listed with reference to the Common Terminology Criteria for Adverse Events v5.0.
There were 311 patients in the ESE group and 395 patients in the LSE group. Reoperation during hospitalization was significantly higher in the LSE group (4.6%) than in the ESE group (1.6%). The total number of days of hospitalization was significantly longer in the LSE group than in the ESE group. However, there was no significant difference in the postoperative complications or ADL at discharge between the 2 groups. In the statistical analysis, preoperative American Society of Anesthesiologists physical status class 3–6, underlying heart or renal disease, and cervical or thoracic spine level of surgical procedures were significantly associated with poor ADL outcomes at discharge.
Spine surgery even for LSE can be safely done, if perioperative risk factors are appropriately managed.
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