Predicting Isocitrate Dehydrogenase Status in Non-Contrast-Enhanced Adult-Type Astrocytic Tumors Using Diffusion Tensor Imaging and 11C-Methionine, 11C-Choline, and 18F-Fluorodeoxyglucose PET.

We aimed to differentiate the isocitrate dehydrogenase (IDH) status among non-enhanced astrocytic tumors using preoperative MRI and PET. We analyzed 82 patients with non-contrast-enhanced, diffuse, supratentorial astrocytic tumors (IDH mutant [IDH-mut], 55 patients; IDH-wildtype [IDH-wt], 27 patients) who underwent MRI and PET between May 2012 and December 2022. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) values using diffusion tensor imaging. We evaluated the tumor/normal brain uptake (T/N) ratios using 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose PET; extracted the parameters with significant differences in distinguishing the IDH status; and verified their diagnostic accuracy. Patients with astrocytomas were significantly younger than those with glioblastomas. The following MRI findings were significant predictors of IDH-wt instead of IDH-mut: thalamus invasion, contralateral cerebral hemisphere invasion, location adjacent to the ventricular walls, higher FA value, and lower MD value. The T/N ratio for all tracers was significantly higher for IDH-wt than for IDH-mut. In a composite diagnosis based on nine parameters, including age, 84.4% of cases with 0-4 points were of IDH-mut; conversely, 100% of cases with 6-9 points were of IDH-wt. Composite diagnosis using all parameters, including MRI and PET findings with significant differences, may help guide treatment decisions for early-stage gliomas.

Posttraumatic epilepsy in chronic disorders of consciousness due to severe traumatic brain injury after traffic accidents.

PURPOSE: To evaluate the clinical state of posttraumatic epilepsy (PTE) in patients with chronic disorders of consciousness (CDC) due to severe traumatic brain injury (STBI) after traffic accidents and clarify the risk factors for seizure occurrence in such patients. METHODS: Two hundred ninety-three patients with CDC due to STBI (mean age at admission [±standard deviation]: 36.4 ± 17.9 years; men: 71.7 %; mean duration of injury to admission: 416 ± 732 days; mean hospitalization time: 899 ± 319 days) were enrolled in this study. We retrospectively investigated the relationship between seizure conditions (type and frequency) and clinical data, including age, sex, pathological types of brain injury, with/without surgical intervention, degree of CDC, and administration of antiseizure medications (ASMs). RESULTS: Overall, 52.9 % (n = 155/293) and 64.2 % of the patients (n = 183/of 285 patients surviving at discharge) were administered ASMs at admission and discharge, respectively. One hundred thirty-two patients (45.1 %) experienced epileptic seizures during hospitalization, and the mean seizure frequency was 4.0 ± 0.4 times per year. In multivariate analysis, significant and independent risk factors of seizure occurrence were revealed to be male sex, high National Agency for Automotive Safety and Victims' Aid score, hypoxic encephalopathy, and history of the neurosurgical operations. CONCLUSION: The high prevalence of PTE in patients with CDC due to STBI, and the significant and independent risk factors for seizure occurrence in the chronic clinical phase were revealed. We expect that this study will aid toward improving clinical assessment and management of epileptic seizures in the population.

Resection of positive tissue on methionine-PET is associated with improved survival in glioblastomas.

BACKGROUND AND PURPOSE: The volume of excised tumor in contrast-enhanced areas evaluated via magnetic resonance imaging is known to have a strong influence on the survival of patients with glioblastoma (GBM). In this study, we investigated the effect of tumor resection on the survival of patients with GBM in the 11 C-methionine (MET) accumulation area using MET-positron emission tomography (MET-PET). METHODS: A total of 26 patients (median age, 69 years; 15 males) who had undergone tumor resection and MET-PET before and after surgery, after being newly diagnosed with GBM, were included in the study. MET-PET before and after tumor resection were compared. The association between the decrease in the maximum standardized uptake value (SUV) of the tumor divided by the normal cortical mean SUV (%; ΔT/N), the MET extent of resection (MET-EOR) from the % reduction in the MET accumulation area (%), and residual MET accumulation area (in cm3 ; MET-residual tumor volume [RTV]), as well as the survival time of patients with GBM, were evaluated via univariate analysis. RESULTS: ΔT/N were positively associated with survival (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.97-0.99], p = .02). MET-RTV revealed a negative association with survival (HR, 1.02 [95% CI, 1.01-1.04], p = .04). Additionally, MET-EOR showed a strong trend with survival (HR, 0.99 [95% CI, 0.97-1.01], p = .06). CONCLUSIONS: Surgical resection of MET-accumulated areas in GBM significantly prolongs the survival of patients with GBM. However, a prospective large-scale multicenter study is needed to confirm our findings.

Combining methionine-PET and MRI fluid-attenuated inversion-recovery mismatch to determine glioma molecular subtype.

BACKGROUND AND PURPOSE: 11 C-methionine (MET)-PET is a useful tool in neuro-oncology. The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign on MRI is a characteristic finding in lower grade gliomas with isocitrate dehydrogenase (IDH) mutations and the absence of the 1p/19q codeletion; however, the T2-FLAIR mismatch sign has low sensitivity in differentiating gliomas and does not aid in identifying glioblastomas with IDH mutations. We therefore investigated the efficacy of the combination of the T2-FLAIR mismatch sign and MET-PET for accurately determining the molecular subtype of gliomas of all grades. METHODS: The present study comprised 208 adult patients diagnosed with supratentorial glioma confirmed by molecular genetics and histopathology. The ratio of the maximum lesion MET accumulation to the mean normal frontal cortex MET accumulation (T/N) was measured. The presence or absence of the T2-FLAIR mismatch sign was determined. The presence or absence of the T2-FLAIR mismatch sign and the MET T/N ratio were compared between glioma subtypes to evaluate individual and combined utility in identifying gliomas with IDH mutations and no 1p/19q codeletion (IDHmut-Noncodel) or gliomas with IDH mutations (IDHmut). RESULTS: The addition of MET-PET to MRI for the presence of the T2-FLAIR mismatch sign improved diagnostic accuracy, with the area under the curve values increasing from .852 to .871 for IDHmut-Noncodel and from .688 to .808 for IDHmut. CONCLUSIONS: The combination of the T2-FLAIR mismatch sign and MET-PET may provide improved diagnostic utility in differentiating gliomas according to molecular subtype, particularly in determining IDH mutation status.

Methionine-PET to differentiate between brain lesions appearing similar on conventional CT/MRI scans.

BACKGROUND AND PURPOSE: 11 C-Methionine (MET)-PET is a useful tool in neuro-oncology. This study aimed to examine whether a combination of diagnostic variables associated with MET uptake could help distinguish between brain lesions that are often difficult to discriminate in conventional CT and MRI. METHODS: MET-PET was assessed in 129 patients with glioblastoma multiforme, primary central nervous lymphoma, metastatic brain tumor, tumefactive multiple sclerosis, or radiation necrosis. The accuracy of the differential diagnosis was analyzed using five diagnostic characteristics in combination: higher maximum standardized uptake value (SUV) of MET in the lesion/the mean normal cortical SUV of MET ratio, overextension beyond gadolinium, peripheral pattern indicating abundant MET accumulation in the peripheral region, central pattern denoting abundant MET accumulation in the central region, and dynamic-up suggesting increased MET accumulation during dynamic study. The analysis was conducted on sets of two of the five brain lesions. RESULTS: Significant differences in the five diagnostic traits were observed among the five brain lesions, and differential diagnosis could be achieved by combining these diagnostic features. The area under the curve between each set of two of the five brain lesions using MET-PET features ranged from .85 to 1.0. CONCLUSIONS: According to the findings, combining the five diagnostic criteria could help with the differential diagnosis of the five brain lesions. MET-PET is an auxiliary diagnostic technique that could help in distinguishing these five brain lesions.

Differentiation of astrocytoma between grades II and III using a combination of methionine positron emission tomography and magnetic resonance spectroscopy.

Objective: This study aimed to establish a method for differentiating between grades II and III astrocytomas using preoperative imaging. Methods: We retrospectively analyzed astrocytic tumors, including 18 grade II astrocytomas (isocitrate dehydrogenase (IDH)-mutant: IDH-wildtype = 8:10) and 56 grade III anaplastic astrocytomas (37:19). We recorded the maximum methionine (MET) uptake ratios (tumor-to-normal: T/N) on positron emission tomography (PET) and three MRS peak ratios: choline (Cho)/creatine (Cr), N-acetyl aspartate (NAA)/Cr, and Cho/NAA, between June 2015 and June 2020. We then evaluated the cut-off values to differentiate between grades II and III. We compared the grading results between contrast enhancement effects on MR and combinational diagnostic methods (CDM) on a scatter chart using the cutoff values of the T/N ratio and MRS parameters. Results: The IDH-mutant group showed significant differences in the Cho/NAA ratio between grades II and III using univariate analysis; however, multiple regression analysis results negated this. The IDH-wildtype group showed no significant differences between the groups. Contrast enhancement effects also showed no significant differences in IDH status. Accordingly, regardless of the IDH status, no statistically independent factors differentiated between grades II and III. However, CDMs showed higher sensitivity and negative predictive value in distinguishing them than MRI contrast examinations for both IDH statuses. We demonstrated a significantly higher diagnostic rate of grade III than of grade II with CDM, which was more striking in the IDH-mutant group than in the wild-type group. Conclusions: CDM could be valuable in differentiating between grade II and III astrocytic tumors.

Brainstem volume, diffusion, and metabolism are associated with chronic consciousness disorders after traumatic brain injury.

BACKGROUND AND PURPOSE: We aimed to identify reliable neuroradiological features of the brainstem reflecting the neurological symptoms of patients with chronic disorders of consciousness (DOCs) due to severe traumatic brain injury (TBI). METHODS: We retrospectively examined 86 patients with chronic DOCs due to severe TBI caused by automobile accidents. We studied the relationships among (1) neurological symptoms, including consciousness level, (2) integrated cognitive/physical condition, and (3) neuroradiological features of the brainstem (brainstem volume on MRI, fractional anisotropy [FA] value in the brainstem, and standardized uptake value [SUV] of 18F-fluorodeoxyglucose [FDG] on positron emission tomography in the brainstem). RESULTS: Brainstem volume was significantly larger and FA values were significantly higher in patients with a better level of consciousness. However, brainstem volumes were significantly decreased and the maximum SUV (SUVmax ) of FDG significantly increased at 2 years following admission regardless of the level of consciousness at admission. The brainstem volume was significantly larger and the FA value and SUVmax of FDG were significantly higher in patients with better National Agency for Automotive Safety and Victims' Aid (NASVA) scores at admission. The decrease in the brainstem volume was significantly minimized and the SUVmax of FDG significantly increased in patients with more improvement in the NASVA score 2 years after admission. CONCLUSIONS: The volume, FA value, and SUVmax of FDG of the brainstem are important neuroradiological features associated with the neurological conditions of patients with chronic DOCs due to severe TBI.

Cerebral Glucose Metabolism in Patients with Chronic Disorders of Consciousness.

OBJECTIVE: To measure regional cerebral metabolic rate of glucose (CMRGlu) in patients with chronic disorders of consciousness (DOCs) using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective cohort study examined 50 patients (mean age: 40.9 ± 20.1 years) with traumatic brain injury (TBI)-induced chronic DOCs [minimally conscious state (MCS)+, n = 20; MCS-, n = 15 and vegetative state (VS), n = 15]. We measured FDG-PET-based CMRGlu values in 12 regions of both brain hemispheres and compared those among MCS+, MCS - and VS patients. RESULTS: In both hemispheres, the regional CMRGlu reduced with consciousness deterioration in 11 of 12 regions (91.7%). In seven right hemisphere regions, CMRGlu values were markedly higher in MCS+ patients than in MCS- patients. Furthermore, CMRGlu was suggestively higher in the left occipital region in MCS- patients than in VS patients. CONCLUSION: Functional preservation in the left occipital region in patients with chronic DOCs might reflect an awareness of external environments, whereas extensive functional preservation in the right cerebral hemisphere might reflect communication motivation.

Spastic muscle stiffness evaluated using ultrasound elastography and evoked electromyogram in patients following severe traumatic brain injury: an observational study.

OBJECTIVE: To determine the relationship between muscle stiffness assessed using ultrasound shear wave elastography, spinal motor neuron excitability assessed using the F wave, and clinical findings of spasticity in patients with spastic muscle overactivity following severe traumatic brain injury. METHODS: This study enrolled 17 inpatients with severe traumatic brain injury and 20 healthy volunteers. Biceps brachii muscle stiffness was then evaluated using ultrasound shear wave speed. Spinal motor neuron excitability was evaluated using the F/M ratio recorded from abductor pollicis brevis muscle. Clinical parameters, such as the modified Ashworth scale and modified Tardieu scale, were assessed in the patient with traumatic brain injury. RESULTS: The patients with traumatic brain injury group had a significantly higher shear wave speed and F/M ratio compared with the healthy group. A higher shear wave speed was correlated with higher clinical spastic severity in patients with traumatic brain injury. The F/M ratio was not significantly correlated with clinical spastic severity. CONCLUSION: Ultrasound shear wave elastography might be helpful for assessing muscle stiffness in patients with spastic muscle overactivity following severe traumatic brain injury. Further studies comprising larger cohorts are warranted.

Radiological Prediction of Isocitrate Dehydrogenase (IDH) Mutational Status and Pathological Verification for Lower-Grade Astrocytomas.

Background and objective The isocitrate dehydrogenase (IDH) status of patients with World Health Organization (WHO) grade II or III astrocytoma is essential for understanding its biological features and determining therapeutic strategies. This study aimed to use radiological analysis to predict the IDH status of patients with lower-grade astrocytomas and to verify the pathological implications. Methods In this study, 47 patients with grade II (17 cases) or III astrocytomas (30 cases), based on 2016 WHO Classification, underwent methionine (MET) positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) on the same day between January 2013 and June 2020. The patients were retrospectively assessed. Immunohistochemistry showed 23 cases of IDH-mutant and 24 of IDH-wildtype. Based on fluid-attenuated recovery inversion (FLAIR)/T2 imaging, three doctors blinded to clinical data independently allocated 18 patients to the clear boundary group between the tumor and the normal brain and 29 to the unclear boundary group. The peak ratios of N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and Cho/NAA and the tumor-to-normal region (T/N) ratio for maximum accumulation in MET-PET were calculated. For statistical analysis, Fisher's exact test was used to assess associations between two variables, and the Mann-Whitney U test to compare the values between the IDH-wildtype and IDH-mutant groups. The optimal cut-off values of MET T/N ratio and MRS parameters for discriminating IDH-wildtype from IDH-mutant were obtained using receiver operating characteristics curves. Results The unclear boundary group had significantly more IDH-wildtype cases than the clear boundary group (P<0.001). The IDH-wildtype group had significantly lower Cho/Cr (<1.84) and Cho/NAA (<1.62) ratios (P=0.02 and P=0.047, respectively) and a higher MET T/N ratio (>1.44, P=0.02) than the IDH-mutant group. The odds for the IDH-wildtype were 0.22 for patients who fulfilled none of the four criteria, including boundary status and three ratios, and 0.9 for all four criteria. Conclusions These results suggest that the combination of MRI, MRS, and MET-PET examination could be helpful for the prediction of IDH status in WHO grade II/III gliomas.

Acupuncture for Chronic Constipation in Patients with Chronic Disorders of Consciousness After Severe Traumatic Brain Injury.

Objective: Patients with chronic disorders of consciousness (DOC) frequently develop chronic constipation. This study evaluated the effects of acupuncture on bowel movements (BMs) in patients with DOC and chronic constipation resulting from severe traumatic brain injury (TBI). Materials and Methods: This retrospective observational study took place in the Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, of Kizawa Memorial Hospital, in Minokamo, Gifu, Japan. The study included 25 patients with chronic DOC resulting from TBI, who received acupuncture treatment. The patients received 2 sessions of acupuncture treatment per week. Information on frequency of defecation, number of days during which patients had BMs, and use of laxatives prior to the acupuncture treatment and after 10 weeks of treatment was extracted from medical records and compared. Results: The median (first quartile and third quartile) frequency of defecation increased significantly after 10 weeks of acupuncture from 3.0 (2.5, 3.5) to 3.5 (2.5, 4.5) times/week (P = 0.038). The number of days on which defecation occurred also increased significantly, from 2.0 (2.0, 2.5) to 2.5 (2.0, 3.5) days/week (P < 0.001). The use of bisacodyl suppositories decreased significantly from 1.5 (1.5, 2.0) to 1.5 (0.5, 2.0) times/week (P = 0.041). The mean ± standard error use of sodium picosulfate for 10 patients decreased significantly, from 20.4 ± 3.5 to 14.3 ± 3.3 drops/week (P = 0.004). Conclusions: Acupuncture treatment could be beneficial for chronic constipation in patients with DOC caused by TBI. A large prospective cohort study with a control group is warranted.

Usefulness of positron emission tomography for differentiating gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system.

OBJECTIVE: Positron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification. METHODS: In total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers. RESULTS: There were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG. CONCLUSIONS: PET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.

Dissociation Between 11C-Methionine-Positron Emission Tomography and Gadolinium-Enhanced Magnetic Resonance Imaging in Longitudinal Features of Glioblastoma After Postoperative Radiotherapy.

The aims of the present study were to compare the longitudinal changes of glioblastoma multiforme after radiotherapy (RT) between 11C-methionine positron emission tomography (MET-PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and to clarify whether these changes were predictive of survival. We included 30 patients, who had undergone MET-PET and Gd-MRI before and every 3 months after RT. The lesion/normal brain uptake (L/N) ratio and contrast-enhancing lesion volume were examined. The L/N ratio was decreased until 9 months after RT with significance until 3 months. The contrast-enhancing lesion volume was decreased until 3 months and thereafter increased until 9 months with significance. The variation rates of the L/N ratio between pre-RT and 3 months differentiated survival of >23 months from ≤23 months. A dissociation could exist in the longitudinal changes of GBM after RT between MET-PET and Gd-MRI. The variation rate of the L/N ratio could be related to survival.

Characteristics of time-activity curves obtained from dynamic 11C-methionine PET in common primary brain tumors.

PURPOSE: The aim of this study was to assess whether dynamic PET with 11C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors. METHODS: One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE). RESULTS: The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P < 0.05). The SLOPE in the late phase was significantly lower in tumors that included an oligodendroglial component compared to astrocytic tumors (P < 0.001). When we set the cutoff of the SLOPE in the late phase to - 0.04 h-1 for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731. CONCLUSIONS: The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

Corrigendum to "Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI".

[This corrects the article DOI: 10.1155/2016/3794029.].

Acupuncture Increases the Excitability of the Cortico-Spinal System in Patients with Chronic Disorders of Consciousness Following Traumatic Brain Injury.

OBJECTIVE: To evaluate the immediate effect of acupuncture on cortico spinal tract (CST) activity in patients with chronic disorders of consciousness (DOC) after traumatic brain injury (TBI) by measuring motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS). DESIGN: Changes in several variables in the acupuncture session were compared with those in the control session without acupuncture in the same patients. SETTING: Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Gifu, Japan. PATIENTS: Fourteen patients (mean age ± standard deviation, 39 ± 17 years; 12 men) with chronic DOC (5 in a vegetative state and 9 in a minimally conscious state) following severe TBI. INTERVENTION: Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes. OUTCOME MEASURES: Main outcome measure was MEP amplitude. MEP amplitude, measured by using TMS on the primary motor cortex, was recorded from the abductor pollicis brevis muscle. MEP recordings were performed before acupuncture (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). As a control, the same procedure without acupuncture was performed on another day with the order randomized. MEP amplitude and latency were calculated. Evoked F-wave measurements were also performed to calculate maximum M-wave amplitude (Mmax), M-wave latency, and F-wave latency in the same muscle. Central motor conduction time (CMCT) and MEP/Mmax ratio were also calculated from the MEP and F-wave measurement data. RESULTS: MEP amplitude and MEP/Mmax were increased significantly in the acupuncture session at phases 1 and 2 compared with the control session (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). CMCTs were reduced at phases 1 and 2 in the acupuncture session compared with the control session, and the change at phase 1 was statistically significant (P = 0.002). CONCLUSIONS: Acupuncture treatment increased the CST activity of patients with chronic DOC after severe TBI.

Acupuncture Reduces Excitability of Spinal Motor Neurons in Patients with Spastic Muscle Overactivity and Chronic Disorder of Consciousness Following Traumatic Brain Injury.

BACKGROUND AND OBJECTIVE: Spastic hypertonia usually occurs in patients with chronic disorders of consciousness (DOC) following severe traumatic brain injury (TBI). Spinal motor neuron excitability has been reported to increase in patients with brain damage. The aim of this study was to evaluate the immediate effects of acupuncture on spinal motor neuron excitability in patients with DOC following TBI by using evoked electromyography. SETTING AND PARTICIPANTS: Eleven male patients (mean age, 33 ± 14 years) with refractory muscle spasticity of the upper extremity accompanying chronic DOC following TBI and admitted to Chubu Medical Center for Prolonged Traumatic Brain Dysfunction were included. DESIGN: A crossover study design was used. Changes in variables in the acupuncture session were compared with those in the control session in the same patients. INTERVENTION: Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes. OUTCOME MEASURES: F-wave was recorded from the abductor pollicis brevis muscle. The main outcome measure was F/M amplitude ratio (F-wave amplitude/M-wave amplitude), calculated as an index for spinal motor neuron excitability. F-waves were recorded before treatment (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). The same procedure was followed in the control session without acupuncture on a separate day. RESULTS: F/M ratio was significantly reduced from baseline to phase 1 (p < 0.001) and phase 2 (p < 0.001) in the acupuncture session, whereas no significant changes were observed in the control session. Changes in F/M ratio from baseline to phase 1 and phase 2 were greater in the acupuncture session than the control session (p = 0.001 and <0.001, respectively). CONCLUSION: The excitability of the spinal motor neurons in patients with DOC following TBI was reduced after acupuncture treatment, suggesting that it is beneficial for reducing spastic muscle hypertonia in these patients.

Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI.

Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage.

Fate of graft cells: what should be clarified for development of mesenchymal stem cell therapy for ischemic stroke?

Mesenchymal stem cells (MSCs) are believed to be promising for cell administration therapy after ischemic stroke. Because of their advantageous characteristics, such as ability of differentiation into neurovascular lineages, avoidance of immunological problems, and abundance of graft cells in mesodermal tissues, studies regarding MSC therapy have increased recently. However, several controversies are yet to be resolved before a worldwide consensus regarding a standard protocol is obtained. In particular, the neuroprotective effects, the rate of cell migration to the lesion, and differentiation direction differ depending on preclinical observations. Analyses of these differences and application of recent developments in stem cell biology or engineering in imaging modality may contribute to identification of criteria for optimal stem cell therapy in which reliable protocols, which control cell quality and include safe administration procedures, are defined for each recovery phase after cerebral ischemia. In this mini review, we examine controversies regarding the fate of grafts and the prospects for advanced therapy that could be obtained through recent developments in stem cell research as direct conversion to neural cells.

Possible involvement of tumor-producing VEGF-A in the recruitment of lymphatic endothelial progenitor cells from bone marrow.

Lymphatic metastasis of human malignant adenocarcinomas is a critical determinant of prognosis. Lymphangiogenesis, the growth of lymphatic vessels, is closely involved in lymphatic metastasis. However, the mechanisms of tumor lymphangiogenesis are not clearly understood. In a previous study, we showed that human gastric cancer MKN45 cells organize neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells in a nude mouse xenograft model. The present results also indicated that human colorectal cancer LS174T and breast cancer SK-BR-3 cells promoted lymphangiogenesis as well as the recruitment of lymphatic endothelial progenitor cells from bone marrow. Among growth factors, which are reported to be involved in lymphangiogenesis, only vascular endothelial growth factor (VEGF)-A was extensively secreted by these three types of adenocarcinoma cells in culture. The well-characterized lymphangiogenic factors VEGF-C and VEGF-D in the culture medium of these three types of adenocarcinoma cells were below the detectable levels in ELISA assay. Secretion of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) was not detected. In in vitro culture assay, VEGF-A directly induced the differentiation of bone marrow mononuclear cells into LYVE-1-positive lymphatic endothelial lineage cells. These data collectively suggest the possibility that VEGF-A-rich human adenocarcinomas induce tumor lymphangiogenesis via recruitment of lymphangiogenic endothelial progenitor cells from bone marrow.