The Safety of Spine Surgery in the Late-Stage Elderly of 75 Years of Age or Older: A Retrospective Multicenter Study.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Spine surgery even for LSE can be safely done, if perioperative risk factors are appropriately managed.

Rehabilitation effects in idiopathic normal pressure hydrocephalus: a randomized controlled trial.

BACKGROUND: Gait-balance disturbances are core symptoms of idiopathic normal pressure hydrocephalus (iNPH). However, the rehabilitation effects of cerebrospinal fluid (CSF) shunting along with other treatment or no further treatment (natural course [NC]) for iNPH are unknown. OBJECTIVES: This study evaluated whether dynamic equilibrium gait training (DEGT) can improve gait-balance functions after CSF shunting of patients with iNPH compared to standard exercise (SE) and NC. Furthermore, it investigated the incidence of falls. METHODS: A total of 70 patients with iNPH who underwent CSF shunting were randomly assigned to 6 weeks of DEGT (n = 23), 6 weeks of SE (n = 23), or NC (n = 24). Evaluation was performed at baseline (preoperatively) and at 1 week, 7 weeks (postintervention), and 6 months postoperatively (follow-up). Outcomes were measured using the functional gait assessment (FGA), 10-m walk test, timed up-and-go test, life-space assessment (LSA), and fall incidence. RESULTS: A total of 65 participants completed the study. During the intention-to-treat analysis, the DEGT group demonstrated significant recovery of gait-balance functions according to only the FGA at postintervention and follow-up compared to the SE and NC groups; however, recovery of the SE group did not differ from that of the NC group. The DEGT group had a significantly lower fall incidence than the other groups at follow-up. Significantly better LSA results were observed for all groups at follow-up compared to baseline; however, no difference in LSA results were observed between groups. CONCLUSIONS: DEGT in addtion to CSF shunting can facilitate the recovery of gait-balance function and reduce the fall incidence of iNPH patients.

Ablation efficacy of 5-aminolevulinic acid-mediated photodynamic therapy on human glioma stem cells.

BACKGROUND: Cancer cells with stem cell-like features are generally more resistant to chemotherapy and radiotherapy than differentiated tumor cells. Thus, these cells tend to increase the propensity for tumor recurrence and metastasis. This study investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in destructing glioma stem cells (GSCs), including the mesenchymal subtype (MES-GSCs) demonstrated to have the lowest radio- and chemosensitivity. METHODS: Five high-grade glioma (HGG) GSC lines and derived differentiated glioma cell (DGC) lines were examined for protoporphyrin-IX (PpIX) expression using fluorescence-activated cell sorting (FACS) and then assessed for ALA-PDT sensitivity using cell viability assays. MES-GSCs surviving ALA-PDT were then isolated and evaluated for stem cell and mesenchymal marker expression levels (CD44, ALDH1A3, KLF4, nestin) by qRT-PCR. The ability of these surviving cells to form tumors was then examined using colony forming and by xenograft tumor assays in athymic mice. Finally, the relationship between PpIX expression level (high versus low) and ALA-PDT sensitivity was examined by FACS and colony forming assays. RESULTS: ALA-PDT was effective against all GSC lines including MES-GSCs. MES-GSC lines exhibited higher PpIX expression than derived DGCs. Surviving MES-GSCs demonstrated lower stem cell marker expression and tumor forming potential than naive MES-GSCs. Higher PpIX production capacity by MES-GSCs was associated with greater colony forming ability, and ALA-PDT was more effective against MES-GSCs with greater PpIX accumulation. CONCLUSION: ALA-PDT may be clinically effective against HGG by targeting GSCs, including MES-GSCs.

Dynamic gait stability in patients with idiopathic normal pressure hydrocephalus with high and low fall-risk.

BACKGROUND: This study aimed to investigate whether dynamic gait stability differs between idiopathic normal-pressure hydrocephalus with high- and low-fall-risk. METHODS: Participants comprised 40 idiopathic normal-pressure hydrocephalus patients and 23 healthy-controls. Idiopathic normal-pressure hydrocephalus patients were divided into those with high-fall-risk (n = 20) and low-fall-risk (n = 20) groups using the cut-off score of ≤14/30 for fall-risk on the Functional Gait Assessment. Dynamic stability during gait was assessed by three-dimensional motion analysis. Dynamic stability was defined as the ability to maintain an extrapolated center of mass within the base of support at heel contact, with the distance between the two defined as the margin of stability. Conscious motor control was assessed by the Movement-Specific Reinvestment Scale. FINDINGS: Anteroposterior and mediolateral margin of stabilities were significantly larger in both idiopathic normal-pressure hydrocephalus groups than in healthy-controls. The mediolateral margin of stability was significantly higher in the high-fall-risk group than in the low-fall-risk group; whereas, the anteroposterior margin of stability did not differ between idiopathic normal-pressure hydrocephalus groups. The Movement-Specific Reinvestment Scale was significantly higher in the high-fall-risk group than in the low-fall-risk group. INTERPRETATION: Idiopathic normal-pressure hydrocephalus patients with have high forward and lateral dynamic stability during gait regardless of their fall-risk. In particular, idiopathic normal-pressure hydrocephalus patients with high-fall-risk may consciously maintain lateral dynamic stability to a greater extent than those with low-fall-risk. These findings highlight a conscious motor control component in the pathological gait of idiopathic normal-pressure hydrocephalus, and provide clues for rehabilitation and fall prevention strategies in idiopathic normal-pressure hydrocephalus patients.

The Characteristic of Light Sources and Fluorescence in the 3-Dimensional Digital Exoscope "ORBEYE" for 5-Aminolevulinic Acid-Induced Fluorescence-Guided Surgery Compared with a Conventional Microscope.

BACKGROUND: The ORBEYE (ORB), an innovative 3-dimensional digital exoscope, is an equipped system for fluorescence-guided surgery with 5-aminolevulinic acid. Therefore, this study aimed to verify the characteristics of fluorescence-guided surgery with 5-aminolevulinic acid and excitation light source with ORB. METHODS: The same operative field of glioblastoma was recorded under blue light (BL) excitation using a conventional microscope (MS) and ORB. For in vitro studies, the energy of 405-nm wavelength light in white light and BL modes of each scope was examined in various focal lengths. To examine the degree of photobleaching with BL for each scope, protoporphyrin IX-soaked filter papers were continuously exposed with BL of an MS and ORB, and the video-recorded red fluorescence intensity was analyzed. RESULTS: The color tone of tumor-induced red fluorescence was remarkably different under each scope. Furthermore, nonfluorescent normal structures without red fluorescence were well recognized under ORB. The energy of 405-nm wavelength light in BL was significantly higher in ORB than that in an MS, especially in the short focal length. With continuous BL excitation to filter papers, the relative red fluorescence intensity of filter papers was significantly decreased over time in ORB than in an MS. In low protoporphyrin IX concentration, the difference was more significant. CONCLUSIONS: With ORB, the good visibility due to BL energy as compared with an MS might improve the surgical manipulation even in BL mode. However, the weak fluorescent tissue and short focal length should be carefully considered because photobleaching might be critical for FGS.

The effect of hypoxia on photodynamic therapy with 5-aminolevulinic acid in malignant gliomas.

BACKGROUND: Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT). MATERIALS AND METHODS: Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O2 21%)-cultured cells (Normoxia-GSCs), and hypoxia (O2 5%)-cultured cells (Hypoxia-GSCs). To compare the effects of different oxygen partial pressures on photoporphyrin Ⅸ (PpⅨ) biosynthetic activity, PpⅨ biosynthetic enzyme and transporter expression levels were examined by qRT-PCR; the intracellular PpⅨ concentration was determined using flow cytometry. Additionally, the sensitivity of these two groups of cells to ALA-PDT was evaluated in vitro. RESULTS: Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert PpⅨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of PpⅨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs. CONCLUSION: Hypoxia-GSCs had lower intracellular PpⅨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of PpⅨ. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.

Weight and Abdominal Pressure-Induced Shunt Trouble in Patients With Shunted Normal Pressure Hydrocephalus: A Comprehensive Study on Pressure Environment of Shunt System.

Objectives: 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. Methods: 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. Results: 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. Conclusion: In patients with shunts, the weight change was linked to ICP via 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.

Corrigendum: Evaluation of the Effectiveness of the Tap Test by Combining the Use of Functional Gait Assessment and Global Rating of Change.

[This corrects the article DOI: 10.3389/fneur.2022.846429.].

Impact of Early Intervention for Idiopathic Normal Pressure Hydrocephalus on Long-Term Prognosis in Prodromal Phase.

Objectives: Because the progression of idiopathic normal pressure hydrocephalus (iNPH) is partially irreversible, we hypothesized that early intervention would markedly improve its prognosis. To test this hypothesis, we retrospectively investigated the long-term prognosis of patients with early intervention in the prodromal phase of iNPH. Methods: We defined the prodromal phase of iNPH as a 3m Timed Up and Go (TUG) of 13.5 s or less and a Mini-Mental State Examination (MMSE) of 24 or more. Of the 83 iNPH patients who underwent shunt surgery at Osaka Medical and Pharmaceutical University Hospital over 3 years from January 2015, 12 prodromal phase cases (73.3 ± 6.2 years, 10 males and 2 females) were included in the study. The iNPH grading scale (INPHGS), MMSE, Frontal Assessment Battery (FAB), intermittent gait disturbance (IGD), social participation status, and development of comorbidities were evaluated over 4 years. Results: Preoperative MMSE was 27.2 ± 1.5, FAB was 14.1 ± 1.8, TUG was 10.7 ± 1.4 s, and total iNPHGS was 2.8 ± 1.4. At 1, 2, 3, and 4 years postoperatively, total INPHGS improved to 0.8, 0.9, 1.5, and 1.7, respectively, and remained significantly better than preoperatively except at 4 years postoperatively. The MMSE improved slightly to 27.5 after 1 year and then declined by 0.35 per year. After 4 years, the mean MMSE was 26.1, and only one patient had an MMSE below 23. FAB improved to 15.2 after 1 year and then declined slowly at 0.85/year. Ten patients (83%) maintained a high capacity for social participation postoperatively. The preoperative tendency to fall and IGD in 9 (75%) and 8 (67%) patients, respectively, completely disappeared postoperatively, resulting in improved mobility. Shunt malfunction associated with four weight fluctuations and one catheter rupture caused temporary worsening of symptoms, which were recovered by valve re-setting and catheter revision, respectively. Conclusion: Early intervention in the prodromal phase of iNPH patients maintained good cognitive and mobility function and social participation ability in the long term. The maintenance of long-term cognitive function suggests its preventive effect on dementia. To realize early intervention for iNPH, it is desirable to establish an early diagnosis system for iNPH.

Evaluation of the Effectiveness of the Tap Test by Combining the Use of Functional Gait Assessment and Global Rating of Change.

Background: Although the tap test for patients with suspected idiopathic normal pressure hydrocephalus (iNPH) is still often performed as part of the preoperative evaluation, it is true that some studies have reported the limitations of the tap test, claiming that it does not provide the additional information for appropriate patient selection for surgery. We aimed to determine whether a better method of pre- and post-tap test assessment could lead to appropriate patient selection for shunting. Methods: We performed the tap test as part of the preoperative evaluation in all 40 patients who underwent lumboperitoneal shunt surgery for iNPH from April 2021 to September 2021. We retrospectively analyzed the patient data. We examined whether a comprehensive evaluation of the effect of the tap test using the Functional Gait Assessment (FGA) and Global Rating of Change (GRC) scales would identify a wider range of patients who would benefit from shunt surgery than the 3-m Timed Up and Go test (TUG) alone. Results: Assuming a prevalence of 1% for iNPH, the TUG had a sensitivity of 0.23, specificity of 0.71, positive likelihood ratio of 0.79, and negative likelihood ratio of 1.09. When improvement in either the FGA or the GRC was used as a criterion for the validity of the tap test, the sensitivity was 0.88, specificity was 0.17, positive likelihood ratio was 1.06, and negative likelihood ratio was 0.71. Conclusion: Improvement in either the FGA or the GRC is a more sensitive criterion for the effectiveness of the tap test for the gait aspect than the TUG. Since the negative likelihood ratio is lower than that for the TUG alone, it is more appropriate to exclude patients with neither FGA nor GRC improvement from surgical indications than to exclude surgical indications based on a negative TUG.

Asymmetry and tuning shift of the cervical vestibular evoked myogenic potential indicate saccular dysfunction in idiopathic normal pressure hydrocephalus.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SIGNIFICANCE: 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.

Dynamic stability during gait in idiopathic normal pressure hydrocephalus and Parkinson's disease.

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.

Perceived and actual changes in gait balance after CSF shunting in idiopathic normal pressure hydrocephalus.

OBJECTIVES: We evaluated the perceived and actual changes in gait and balance function immediately after cerebrospinal fluid (CSF) shunting in patients with idiopathic normal pressure hydrocephalus (iNPH), including those with mild cases. MATERIALS AND METHODS: Ninety-nine iNPH patients were assessed using the timed Up and Go (TUG) and Functional Gait Assessment (FGA) before and 1-week after CSF shunting and their perceived changes were assessed on a Global Rate of Change (GRC) scale. Minimal clinically important differences (MCIDs) were calculated using a receiver operating characteristic (ROC) curve method using GRC scores. RESULTS: In all patients (n = 99), the TUG value postoperatively was significantly faster than the preoperative value (difference; 3.1 ± 4.6 s, p < 0.001), and the postoperative FGA score was significantly better than the preoperative score (difference; 3.8 ± 3.3 points, p < 0.001). In the TUG <15 s group (n = 51), the postoperative FGA score was significantly improved (difference; 3.3 ± 2.9 points, p < 0.001), whereas the TUG value was only slightly improved (difference; 0.6 ± 1.6 s, p = 0.008). The ROC curve MCIDs of GRC ≥2 points, which is the recommended level of improvement, were 1.7 s (16.5%) for the TUG and 4 points (20.0%) for the FGA in all patients (n = 99) and the TUG <15 s group (n = 51). CONCLUSIONS: FGA can be used to confirm treatment effects, including perceived and actual changes after CSF shunting, in patients with mild iNPH. Our results can help clinicians to determine the clinical significance of improvements in gait and balance function immediately after CSF shunting in individual patients with iNPH.

Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus.

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.

A multi-center, prospective study on the progression rate of asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on magnetic resonance imaging to idiopathic normal pressure hydrocephalus.

INTRODUCTION: Our previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors. METHODS: We conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as "asymptomatic ventriculomegaly with features of iNPH on MRI"; in the present study, asymptomatic was defined as "0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS)." We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values. RESULTS: In 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression. CONCLUSIONS: The multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

Long-Term Prognosis of Cognitive Function in Patients With Idiopathic Normal Pressure Hydrocephalus After Shunt Surgery.

The long-term prognosis of cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH) remains unclear. This study aimed to determine the long-term prognosis of cognitive function in patients with iNPH, as well as the factors related to it. It included 48 patients with iNPH who were treated with cerebrospinal fluid shunting between January 2015 and December 2017 at Osaka Medical College Hospital, with follow-up evaluation of their cognitive function for >2 years. Cognitive function was measured using the Mini-Mental State Examination (MMSE) preoperatively and at 3 months, 1 and 2 years post-operatively. The mean MMSE score (22.4 ± 5.4 preoperatively) improved at 3 months [23.8 ± 5.0 (p = 0.0002)] and 1 year [23.7 ± 4.8 (p = 0.004)] post-operatively. At 2 years post-operatively, they were able to maintain their preoperative level (22.6 ± 5.3). The patients were classified in to the cognitive decline group [11 (23%) patients; a decrease in the MMSE score by ≥ 2 points 2 years after surgery] and the maintenance/improvement group [37 (77%) patients]. Univariate and receiver operating characteristic analyses were performed for the two groups to identify factors associated with cognitive prognosis. In both groups, the patients who were younger (p = 0.009) or had milder symptoms (p = 0.035) had a better long-term prognosis of cognitive function. The cutoffs for age and disease severity (idiopathic normal-pressure hydrocephalus grading scale; INPHGS) were 78 years (area under the curve = 0.77) and 5 points (area under the curve = 0.71), respectively. In conclusion, most patients (77%) were able to improve and maintain cognitive function for at least 2 years after surgery. The fact that disease severity and age are associated with cognitive prognosis suggests that early iNPH intervention is desirable to improve cognitive prognosis.

Singlet oxygen model evaluation of interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor.

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.

[The Efficacy of the Emergent Shunt-Clamp System for Secondary Hydrocephalus Associated with Fourth Ventricle Outlet Obstruction Syndrome:A Report of Two Cases].

Endoscopic third ventriculostomy(ETV)is the first-line treatment for fourth ventricle outlet obstruction(FVOO)-associated hydrocephalus. However, because FVOO is difficult to diagnose in the acute stage, ventriculoperitoneal shunt(VPS)is also used. Herein, we report two cases of shunted FVOO resulting in overdrainage or slit ventricle syndrome(SVS)that were treated successfully with the shunt-clamp system. In addition, we discuss the efficacy of the shunt-clamp system for FVOO-associated hydrocephalus. CASE 1:A 79-year-old man complained of severe postural headaches. One year earlier, he underwent VPS for secondary hydrocephalus associated with hemorrhagic cerebellar infarction. CT revealed that the ventricle had become slit-like. Although the shunt valve adjusted the maximum pressure, his complaint and the ventricle shape did not improve. After the on-off valve was inserted in the shunt system and clamped, his symptoms were resolved and the ventricle size was normalized. CASE 2:A 21-year-old man who complained of drowsiness, diplopia, and severe intermittent retroocular pain was admitted to our hospital. One year earlier, he underwent VPS with the shunt-clamp system for a secondary hydrocephalus after surgery for medulloblastoma. CT on admission revealed ventricle dilatation;however, the shape of the ventricle became slit-like 3 days after admission. We made a diagnosis of SVS and planned ETV. Owing to the difficulty in approaching the lateral ventricle, the shunt system was clamped 8 hours before the operation. After confirming ventricle dilatation, ETV was successfully performed. After the operation, the symptoms were resolved, and magnetic resonance imaging confirmed that the ventricle size was normalized.

Associations among falls, gait variability, and balance function in idiopathic normal pressure hydrocephalus.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.