Motor-cognitive functions required for driving in post-stroke individuals identified via machine-learning analysis.

BACKGROUND: People who were previously hospitalised with stroke may have difficulty operating a motor vehicle, and their driving aptitude needs to be evaluated to prevent traffic accidents in today's car-based society. Although the association between motor-cognitive functions and driving aptitude has been extensively studied, motor-cognitive functions required for driving have not been elucidated. METHODS: In this paper, we propose a machine-learning algorithm that introduces sparse regularization to automatically select driving aptitude-related indices from 65 input indices obtained from 10 tests of motor-cognitive function conducted on 55 participants with stroke. Indices related to driving aptitude and their required tests can be identified based on the output probability of the presence or absence of driving aptitude to provide evidence for identifying subjects who must undergo the on-road driving test. We also analyzed the importance of the indices of motor-cognitive function tests in evaluating driving aptitude to further clarify the relationship between motor-cognitive function and driving aptitude. RESULTS: The experimental results showed that the proposed method achieved predictive evaluation of the presence or absence of driving aptitude with high accuracy (area under curve 0.946) and identified a group of indices of motor-cognitive function tests that are strongly related to driving aptitude. CONCLUSIONS: The proposed method is able to effectively and accurately unravel driving-related motor-cognitive functions from a panoply of test results, allowing for autonomous evaluation of driving aptitude in post-stroke individuals. This has the potential to reduce the number of screening tests required and the corresponding clinical workload, further improving personal and public safety and the quality of life of individuals with stroke.

Increased cerebrovascular reactivity in selected brain regions after extracranial-intracranial bypass improves the speed and accuracy of visual cancellation in patients with severe steno-occlusive disease: a preliminary study.

The effect of the change in cerebrovascular reactivity (CVR) in each brain area on cognitive function after extracranial-intracranial bypass (EC-IC bypass) was examined. Eighteen patients who underwent EC-IC bypass for severe unilateral steno-occlusive disease were included. Single-photon emission CT (SPECT) for evaluating CVR and the visual cancellation (VC) task were performed before and after surgery. The accuracy of VC was expressed by the arithmetic mean of the age-matched correct answer rate and the accurate answer rate, and the averages of the time (time score) and accuracy (accuracy score) of the four VC subtests were used. The speed of VC tended to be slower, whereas accuracy was maintained before surgery. The EC-IC bypass improved CVR mainly in the cerebral hemisphere on the surgical side. On bivariate analysis, when CVR increased post-operatively, accuracy improved on both surgical sides, but the time score was faster on the left and slower on the right surgical side. Stepwise multiple regression analysis showed that the number of the brain regions associated with the time score was 5 and that associated with the accuracy score was 4. In the hemodynamically ischemic brain, processing speed might be adjusted so that accuracy would be maintained based on the speed-accuracy trade-off mechanism that may become engaged separately in the left and right cerebral hemispheres when performing VC. When considering the treatment for hemodynamic ischemia, the relationship between CVR change and the speed-accuracy trade-off in each brain region should be considered.

The right hemisphere is important for driving-related cognitive function after stroke.

Considering quality of life (QOL) after stroke, car driving is one of the most important abilities for returning to the community. In this study, directed attention and sustained attention, which are thought to be crucial for driving, were examined. Identification of specific brain structure abnormalities associated with post-stroke cognitive dysfunction related to driving ability would help in determining fitness for car driving after stroke. Magnetic resonance imaging was performed in 57 post-stroke patients (51 men; mean age, 63 ± 11 years) who were assessed for attention deficit using a standardized test (the Clinical Assessment for Attention, CAT), which includes a Continuous Performance Test (CPT)-simple version (CPT-SRT), the Behavioral Inattention Test (BIT), and a driving simulator (handle task for dividing attention, and simple and selective reaction times for sustained attention). A statistical non-parametric map (SnPM) that displayed the association between lesion location and cognitive function for car driving was created. From the SnPM analysis, the overlay plots were localized to the right hemisphere during handling the hit task for bilateral sides (left hemisphere damage related to right-side neglect and right hemisphere damage related to left-side neglect) and during simple and selective reaction times (false recognition was related to damage of both hemispheres). A stepwise multiple linear regression analysis confirmed the importance of both hemispheres, especially the right hemisphere, for cognitive function and car driving ability. The present study demonstrated that the right hemisphere has a crucial role for maintaining directed attention and sustained attention, which maintain car driving ability, improving QOL for stroke survivors.

Prognostic importance of temozolomide-induced neutropenia in glioblastoma, IDH-wildtype patients.

Standard treatment for patients with primary glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Recent reports have demonstrated that TMZ-induced myelosuppression correlates with survival in patients with GBM. However, those results were evaluated before the 2016 revision of the World Health Organization classification. This study examined whether myelosuppression during concomitant TMZ phase correlates with prognosis in GBM, IDH-wildtype patients. We examined circulating blood cell counts in 50 patients with GBM, IDH-wildtype who received the standard treatment protocol between August 2005 and November 2015. We assessed relationships between rates of decrease in blood cells (white blood cells (WBC), neutrophils, lymphocytes, red blood cells, and platelets) during the concomitant TMZ phase and overall survival (OS) using univariate and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) status). Log-rank testing revealed that age, KPS, extent of resection, MGMT status, and decrease rates of WBC, neutrophils, and platelets correlated significantly with OS. On multivariate analysis, age, MGMT status, and decrease rate of neutrophils correlated significantly with OS. Patients with a ≥ 40% decrease in neutrophils showed significantly longer OS than those with < 40% (hazard ratio = 2.815; 95% confidence interval = 1.177-7.038; P = 0.0196). A decrease of ≥ 40% in neutrophils represents a predictor of good prognosis for GBM, IDH-wildtype. Blood cell counts during the concomitant TMZ phase can help predict OS in patients with GBM, IDH-wildtype receiving the standard treatment protocol.

Neuroanatomic pathways associated with monoaminergic dysregulation after stroke.

OBJECTIVE: We examined the complex relationship between lesion location, symptoms of depression (affective and apathetic), and monoamine dysfunction after stroke. METHODS: Magnetic resonance imaging was performed on 48 post-stroke patients that had been assessed for affective and apathetic symptoms using the Hospital Anxiety and Depression Scale and the Apathy Scale, respectively. Noradrenalin (NA), dopamine (DA), their metabolites, and a metabolite of serotonin (5-HT) were measured using 24-h urine samples, and 5-HT and 3-methoxy-4-hydroxyphenylglycol were measured using blood samples. We developed a statistical parametric map that displayed the associations between lesion location and both positive and negative alterations of monoamines and their metabolites. RESULTS: Multivariate analysis indicated that basal ganglia lesions and 5-HT showed relationships with affective symptoms, whereas homovanillic acid was related to apathetic symptoms. Univariate analysis showed no such relationships. However, decreases in NA and DA and increases in NA and DA turnover were related to lesions in the brainstem, whereas increases in NA and DA as well as decreases in NA and DA turnover were related to cortical and/or striatum lesions. 5-HT turnover data showed a pattern opposite to that seen for NA and DA turnover. CONCLUSIONS: Monoaminergic neuronal pathways are controlled by both receptor-mediated feedback mechanisms and turnover; thus, depletion of monoamines is not the only cause of depression and apathy. Moreover, the monoamine neuronal network might be divided into two branches, catecholamine (NA and DA) and 5-HT, both of which are anatomically and functionally interconnected and could respectively influence apathetic and affective symptoms of depression.

p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation Associated with Survivin Downregulation in Glioma Cells.

OBJECTIVE: In human glioma cells, p16 gene transfer induced G1/S arrest, increased radiosensitivity and abnormal nucleation (especially bi- and multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and an increase in aneuploidy accompanied by centrosome amplification. Abnormal nucleation and aneuploidy represent chromosome instability (CIN), and it is well known that centrosome amplification leads to CIN. However, little has been reported that suggests that transferring p16 causes centrosome overduplication during the G1/S phase. METHODS: The p16 gene was transferred into p16-null human glioma cell lines (U251MG and D54MG) using adenovirus with or without irradiation. Centrosome amplification was evaluated by immunofluorescence. We also investigated the DNA replication licensing factor CDT1, its inhibitor geminin and survivin expression as regulators of chromosomal segregation. RESULTS: p16 gene transfer with radiation initiated the greatest degree of centrosome overduplication. CDT1 showed low levels, geminin was unchanged and survivin decreased in Ax-hp16-infected cells with radiation. Those changes of factors affecting DNA licensing or chromosomal segregation might contribute to CIN. CONCLUSION: p16 transfer caused centrosome amplification even in G1/S phase-arrested cells. This suggests that p16 is involved in abnormal nucleation and radiosensitization in human glioma cells. © 2015 S. Karger AG, Basel.

Neuroanatomic pathways associated with poststroke affective and apathetic depression.

OBJECTIVES: Our goal was to localize lesions in poststroke depression patients using magnetic resonance imaging, based on the statistical parametric maps image analysis technique that can be used to combine image data from multiple participants and correlate these images with other data sets. METHODS: Magnetic resonance imaging acquisitions were obtained from 149 poststroke patients, who were assessed for affective and apathetic symptoms using the Hospital Anxiety and Depression Scale and the Apathy Scale, respectively. We created a statistical parametric map that displayed an association between lesion location and affective and apathetic symptoms. RESULTS: Among the patients with higher depressive scores, the lesion overlap centered on the brainstem, left basal ganglia, and left frontal cortex. Among the patients with higher apathy scores, the lesion overlap centered on the brainstem and bilateral striatum. The overlap lesion for both affective and apathetic depression centered mainly on the brainstem; however, the two types of depression often did not overlap. CONCLUSIONS: Two core symptoms that can occur after stroke, affective and apathetic symptoms, appear to be associated with different monoaminergic neuroanatomic pathways (serotonergic and dopaminergic).

Carotid arterial intraplaque hemorrhage and calcification influences cerebral hemodynamics.

We evaluated associations between cerebral blood flow (CBF) and histopathological features in atherosclerotic lesions of the internal carotid artery. Cerebrovascular reactivity (CVR) and CBF were measured in 72 patients with unilateral carotid artery stenosis who underwent Xe-CT before carotid endarterectomy. Collateral blood flow was estimated as stump pressure. Proportions of fibrous tissue, intraplaque hemorrhage (IPH), and calcification were pathologically compared with the entire plaque body. The Spearman's rank test and stepwise multiple linear regression analysis revealed that the IPH rate significantly and negatively correlated with CBF, whereas the calcification rate positively correlated with CVR. One-way analysis of variance showed that IPH and the absence of calcification might confer a risk for CBF and CVR reduction. Thus, not only the stenosis rate but also the degree of IPH and calcification in carotid arterial plaque are notable risk factors for ischemic stroke.

Vertical dynamic visual acuity is significantly lower than horizontal dynamic visual acuity.

Dynamic visual acuity (DVA) is crucial for the perception of moving objects. While traditional DVA assessment tools predominantly focus on horizontal movements, the evaluation of vertical DVA remains unstandardized. Consequently, the disparities between vertical and horizontal DVAs are yet to be thoroughly investigated. Therefore, we designed a system capable of conducting multidirectional DVA tests and eye movement measurements. During the experiments, the participants identified the gap direction of the Landolt-C ring moving either horizontally or vertically. The speed of movement decelerated from its maximum as a high-speed infrared camera captured the pupil movements of the left eye at 500 fps. We conducted tests on 15 healthy university students (aged [Formula: see text] years) and measured vertical and horizontal DVAs five times each. DVA was deduced from the Landolt-C ring speed with accurate gap direction responses, and eye movement was assessed based on the total gaze movement distance. The results revealed superior DVA and eye movement in the horizontal direction compared with the vertical direction ([Formula: see text]). This highlights the anisotropic characteristics of DVA and eye movement. The proposed system has the potential for multidirectional dynamic vision evaluation and training in clinical scenarios.

Growth hormone receptor expression in brain tumors.

Growth hormone (GH) is essential for quality of life in both children and adults, but it is also believed to enhance the growth of various neoplasms. However, the role of GH in the brain, particularly in brain tumors, has yet to be established. To clarify these problems from the perspective of receptor expression, we examined GH receptor (GHR) expression in brain tumors using immunohistochemistry and the correlation between GHR expression and clinical features. Surgical specimens obtained from patients with brain tumors (106 pituitary adenomas, 12 craniopharyngiomas, 13 germ cell tumors, 6 medulloblastomas, and 12 malignant gliomas) were examined immunohistochemically for GHR expression. The GHR positive rate was lower in malignant tumors than in benign tumors (59% in pituitary adenomas, 73% in craniopharyngiomas, 23% in germ cell tumors, and 0% in medulloblastomas and gliomas). GHR staining in pituitary adenomas was weaker than that in normal pituitary gland. Among the GH-producing pituitary adenomas, there was no difference in size between GHR-positive and -negative tumors. However, among the non-GH-producing adenomas, GHR-positive tumors were significantly smaller. Thus, immunohistochemical GHR expression may have, at least in part, a negative impact on tumor growth potential in brain tumors.

Projection of Damaged Visual and Language Regions on Low Trail Making Test Part-B Performance in Stroke Patients.

Background: The Trail Making Test Part-B (TMT-B) is an attention functional test to investigate cognitive dysfunction. It requires the ability to recognize not only numbers but also letters. We analyzed the relationship between brain lesions in stroke patients and their TMT-B performance. Methods: From the TMT-B, two parameters (score and completion time) were obtained. The subjects were classified into several relevant groups by their scores and completion times through a data-driven analysis (k-means clustering). The score-classified groups were characterized by low (≤10), moderate (10 < score < 25), and high (25) scores. In terms of the completion time, the subjects were classified into four groups. The lesion degree in the brain was calculated for each of the 116 regions classified by automated anatomical labeling (AAL). For each group, brain sites with a significant difference (corrected p < 0.1) between each of the 116 regions were determined by a Wilcoxon Rank-Sum significant difference test. Results: Lesions at the cuneus and the superior occipital gyrus, which are mostly involved in visual processing, were significant (corrected p < 0.1) in the low-score group. Furthermore, the moderate-score group showed more-severe lesion degrees (corrected p < 0.05) in the regions responsible for the linguistic functions, such as the superior temporal gyrus and the supramarginal gyrus. As for the completion times, lesions in the calcarine, the cuneus, and related regions were significant (corrected p < 0.1) in the fastest group as compared to the slowest group. These regions are also involved in visual processing. Conclusion: The TMT-B results revealed that the subjects in the low-score group or the slowest- group mainly had damage in the visual area, whereas the subjects in the moderate-score group mainly had damage in the language area. These results suggest the potential utility of TMT-B performance in the lesion site.

Artificially-reconstructed brain images with stroke lesions from non-imaging data: modeling in categorized patients based on lesion occurrence and sparsity.

Brain imaging is necessary for understanding disease symptoms, including stroke. However, frequent imaging procedures encounter practical limitations. Estimating the brain information (e.g., lesions) without imaging sessions is beneficial for this scenario. Prospective estimating variables are non-imaging data collected from standard tests. Therefore, the current study aims to examine the variable feasibility for modelling lesion locations. Heterogeneous variables were employed in the multivariate logistic regression. Furthermore, patients were categorized (i.e., unsupervised clustering through k-means method) by the charasteristics of lesion occurrence (i.e., ratio between the lesioned and total regions) and sparsity (i.e., density measure of lesion occurrences across regions). Considering those charasteristics in models improved estimation performances. Lesions (116 regions in Automated Anatomical Labeling) were adequately predicted (sensitivity: 80.0-87.5% in median). We confirmed that the usability of models was extendable to different resolution levels in the brain region of interest (e.g., lobes, hemispheres). Patients' charateristics (i.e., occurrence and sparsity) might also be explained by the non-imaging data as well. Advantages of the current approach can be experienced by any patients (i.e., with or without imaging sessions) in any clinical facilities (i.e., with or without imaging instrumentation).

Post-operative hyponatremia in patients with pituitary adenoma: post-operative management with a uniform treatment protocol.

This study is a retrospective analysis of hyponatremia after transsphenoidal surgery in patients with pituitary adenoma. We evaluated (i) the incidence of post-operative hyponatremia (serum Na levels ≤ 135 mEq/L) and the emergence of hyponatremic symptoms, and assessed (ii) the risk factors under a uniform protocol of i.v. infusion with steroid and electrolyte fluid. We examined 88 consecutive operated patients (female: 60; male: 28) with pituitary adenoma. Apart from reconfirming the effects of the purported risk factors, we focused on the degree of serum Na decline on post-operative hyponatremia. Although remained stable during early post-operative period (4 days after surgery), the serum Na levels subsequently decreased after post-operative day 4 in 81 of 88 cases (92.0%). Of 88 patients, 27 (30.7%) and 9 (10.2%) cases suffered from hyponatremia, and developed hyponatremic symptoms. Interestingly, the degree of serum Na levels decline (from pre-operative levels) indicated a useful independent risk factor for monitoring hyponatremic symptoms (p = 0.006) and the degree of decline tended to be greater in elder patients (> 60 years) (p = 0.0346). Serum Na levels should be monitored from, at least, post-operative day 7 to detect early development of hyponatremia. Special attention and recovery effort should be given to elder patients with marked serum Na level decline after surgery.

Post-stroke depression and apathy: Interactions between functional recovery, lesion location, and emotional response.

Depression and apathy are often observed after stroke and are often confused with one another. In the present review, we argue that the current concept of 'post-stroke depression' (PSD) in fact consists of two core symptoms or syndromes: (i) affective (depressive) PSD; and (ii) apathetic PSD. We argue that these two core symptoms are each associated with a different underlying neuroanatomical mechanism, a pattern that influences functional recovery. Post-stroke disabilities can provoke several distinct emotional responses, some of which are associated with severe depression. We examined one of these emotional responses previously, namely 'insistence on recovery', which was believed to be a negative indicator of functional improvement in disabled stroke patients. However, an appropriate level of insistence on recovery may, in fact, be associated with reduced depression and apathy, resulting in enhanced recovery from stroke-related disabilities. Improvements in physical disabilities (trunk stability or activities of daily living, such as walking) also reduce depression and apathy. Therefore, the experience of PSD/apathy may be intertwined with various initial emotional responses and improvements in physical functioning. Effective treatment of PSD/apathy requires a multidisciplinary approach, such that neuroanatomical/neurobiological, emotional, and physical (rehabilitation) domains are all addressed.

Pen-point Trajectory Analysis During Trail Making Test Based on a Time Base Generator Model.

The Trail Making test (TMT) is a widely used neuropsychological test to assess the cognitive function of patients. This paper presents the analysis method of pen-point trajectory during the TMT based on a time base generator (TBG). In the proposed method, the movement segments between targets are first extracted from pen-point trajectories, which are measured during performance of the TMT on an iPad. By fitting the extracted trajectories with a TBG-based trajectory generation model, the proposed method can then calculate quantitative indices representing the shape and collapse of the velocity profile. In the experiment, we analyzed TMT data from 25 stroke patients who were classified into three groups according to their scores on the Mini-Mental State Examination (MMSE). The results revealed that most of the measured inter-target trajectories had unimodal bell-shaped velocity profiles, as seen in reaching movements. Furthermore, we found that the degree of collapse in the velocity profile shape increased significantly when the cognitive function decreased.

Vulnerable carotid arterial plaque causing repeated ischemic stroke can be detected with B-mode ultrasonography as a mobile component: Jellyfish sign.

Mobile plaque is associated with increased risk of ischemic stroke, but definitions have remained unclear. We have previously reported that carotid ultrasonography can detect the mobile component of the carotid plaque surface, which rises and falls in a manner inconsistent with arterial pulsatile wall motion (Jellyfish sign). However, clinical and pathological features of Jellyfish sign remain unclear. The subjects comprised of 165 patients with carotid plaque and degree of area stenosis ≥50% on ultrasonography. Using magnetic resonance imaging, we quantified intraplaque hemorrhage (IPH) and defined ischemic stroke in each patient. Fifteen surgical specimens were obtained by carotid endarterectomy, and pathological features (area of fibrous cap and intraplaque atheromatous lesion) were compared with ultrasonographic plaque surface movement rate. Carotid plaques with IPH were seen in 78 cases, with Jellyfish sign in 31 cases. Jellyfish sign was not detected in patients without IPH. In these 15 patients, the fibrous cap covered the atheromatous lesion, and cap thickness correlated negatively with Jellyfish-positive plaque surface movement rate. Kaplan-Meier and Cox multiple regression analysis demonstrated that the most important predictor of ischemic stroke during follow-up is Jellyfish sign, not IPH. Stroke events in patients with Jellyfish sign repeated within a short interval after diagnosis. Jellyfish sign on ultrasonography is a sign of high-risk plaque vulnerability, suggesting rupture of the fibrous cap associated with the release of thrombogenic factors into the arterial lumen, and resulting in repeated ischemic stroke during a short interval after diagnosis.

Relationships between motor and cognitive functions and subsequent post-stroke mood disorders revealed by machine learning analysis.

Mood disorders (e.g. depression, apathy, and anxiety) are often observed in stroke patients, exhibiting a negative impact on functional recovery associated with various physical disorders and cognitive dysfunction. Consequently, post-stroke symptoms are complex and difficult to understand. In this study, we aimed to clarify the cross-sectional relationship between mood disorders and motor/cognitive functions in stroke patients. An artificial neural network architecture was devised to predict three types of mood disorders from 36 evaluation indices obtained from functional, physical, and cognitive tests on 274 patients. The relationship between mood disorders and motor/cognitive functions were comprehensively analysed by performing input dimensionality reduction for the neural network. The receiver operating characteristic curve from the prediction exhibited a moderate to high area under the curve above 0.85. Moreover, the input dimensionality reduction retrieved the evaluation indices that are more strongly related to mood disorders. The analysis results suggest a stress threshold hypothesis, in which stroke-induced lesions promote stress vulnerability and may trigger mood disorders.

Lesions in the right Rolandic operculum are associated with self-rating affective and apathetic depressive symptoms for post-stroke patients.

Stroke survivors majorly suffered from post-stroke depression (PSD). The PSD diagnosis is commonly performed based on the clinical cut-off for psychometric inventories. However, we hypothesized that PSD involves spectrum symptoms (e.g., apathy, depression, anxiety, and stress domains) and severity levels. Therefore, instead of using the clinical cut-off, we suggested a data-driven analysis to interpret patient spectrum conditions. The patients' psychological conditions were categorized in an unsupervised manner using the k-means clustering method, and the relationships between psychological conditions and quantitative lesion degrees were evaluated. This study involved one hundred sixty-five patient data; all patients were able to understand and perform self-rating psychological conditions (i.e., no aphasia). Four severity levels-low, low-to-moderate, moderate-to-high, and high-were observed for each combination of two psychological domains. Patients with worse conditions showed the significantly greater lesion degree at the right Rolandic operculum (part of Brodmann area 43). The dissimilarities between stress and other domains were also suggested. Patients with high stress were specifically associated with lesions in the left thalamus. Impaired emotion processing and stress-affected functions have been frequently related to those lesion regions. Those lesions were also robust and localized, suggesting the possibility of an objective for predicting psychological conditions from brain lesions.

Cerebrospinal fluid ctDNA and metabolites are informative biomarkers for the evaluation of CNS germ cell tumors.

Serum and cerebrospinal fluid (CSF) levels of α-fetoprotein and ß-subunit of human chorionic gonadotropin are used as biomarkers for the management of central nervous system (CNS) germ cell tumors (GCTs). However, additional discriminating biomarkers are required. Especially, biomarkers to differentiate non-germinomatous germ cell tumors (NGGCTs) from germinomas are critical, as these have a distinct prognosis. We investigated CSF samples from 12 patients with CNS-GCT patients (8 germinomas and 4 NGGCTs). We analyzed circulating tumor DNA (ctDNA) in CSF to detect mutated genes. We also used liquid chromatography-mass spectrometry to characterize metabolites in CSF. We detected KIT and/or NRAS mutation, known as frequently mutated genes in GCTs, in 3/12 (25%) patients. We also found significant differences in the abundance of 15 metabolites between control and GCT, with unsupervised hierarchical clustering analysis. Metabolites related to the TCA cycle were increased in GCTs. Urea, ornithine, and short-chain acylcarnitines were decreased in GCTs. Moreover, we also detected several metabolites (e.g., betaine, guanidine acetic acid, and 2-aminoheptanoic acid) that displayed significant differences in abundance in patients with germinomas and NGGCTs. Our results suggest that ctDNA and metabolites in CSF can serve as novel biomarkers for CNS-GCTs and can be useful to differentiate germinomas from NGGCTs.

The combination of low cytoplasmic and high nuclear expression of p27 predicts a better prognosis in high-grade astrocytoma.

BACKGROUND: The function of the cyclin-dependent kinase (cdk) inhibitor p27 is regulated by translocation between the nucleus (activate) and the cytosol (inactivate). No previous reports have examined the subcellular localization of p27 in glioma which was evaluated here regarding the prognosis in high-grade astrocytomas. PATIENTS AND METHODS: The pattern of subcellular localization of p27 expression was examined immunohistochemically in 49 patients with high-grade astrocytoma who were over 20 years of age. The relationship between p27 localization and the prognosis was statistically examined. RESULTS: Kaplan-Meier survival analysis showed that cytoplasmic p27 expression was statistically associated with a worse prognosis (p = 0.0203), while nuclear p27 expression showed some tendency towards a better prognosis (p = 0.1180). Cox multiple regression analysis showed the combination of high nuclear and low cytoplasmic p27 expression associated with a significantly better prognosis in high-grade astrocytoma. CONCLUSION: A combination of low cytoplasmic and high nuclear expression of p27 predicts a better prognosis in high-grade astrocytomas and thus the subcellular localization of p27 expression is useful for predicting the prognosis for these patients.