Prediction of voluntary movements of the upper extremities by resting state-brain regional glucose metabolism in patients with chronic severe brain injury: A pilot study.

Confirmation of the exact voluntary movements of patients with disorder of consciousness following severe traumatic brain injury (TBI) is difficult because of the associated communication disturbances. In this pilot study, we investigated whether regional brain glucose metabolism assessed by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) at rest could predict voluntary movement in severe TBI patients, particularly those with sufficient upper limb capacity to use communication devices. We visually and verbally instructed patients to clasp or open their hands. After video capture, three independent rehabilitation therapists determined whether the patients' movements were voluntary or involuntary. The results were compared with the standardized uptake value in the primary motor cortex, referring to the Penfield's homunculus, by resting state by FDG-PET imaged 1 year prior. Results showed that glucose uptake in the left (p = 0.0015) and right (p = 0.0121) proximal limb of the primary motor cortex, based on Penfield's homunculus on cerebral cartography, may reflect contralateral voluntary movement. Receiver operating characteristic curve analysis showed that a mean cutoff standardized uptake value of 5.47 ± 0.08 provided the best sensitivity and specificity for differentiating between voluntary and involuntary movements in each area. FDG-PET may be a useful and robust biomarker for predicting long-term recovery of motor function in severe TBI patients with disorders of consciousness.

Longitudinal CT evaluation of transdermal scopolamine for aspiration pneumonia with sialorrhea in severe chronic brain injury: A case series.

Sialorrhea is a major cause of recurrent aspiration pneumonia in severe chronic brain injury. Previous reports have shown that transdermal scopolamine can decrease saliva production. We present four patients with severe chronic brain injury who experienced repeat aspiration pneumonia with sialorrhea. Longitudinal computed tomography examinations to assess the therapeutic effect were performed in all four cases before and after transdermal scopolamine. Transdermal scopolamine was applied as a patch (0.1 g/2.5 cm2) behind the earlobe every 24 h after confirming the absence of glaucoma. Patches were formulated as an in-hospital preparation (scopolamine butylbromide 0.25 g and hydrophilic cream 4.75 g) under the approval of our institutional review board. Longitudinal computed tomography after transdermal scopolamine use showed a decrease in pleural effusions associated with continuous aspiration pneumonia in all four cases. The data from repeat computed tomography suggest that long-term transdermal scopolamine for reducing saliva production may be a reasonable option for appropriate palliative care in severe chronic brain injury patients.

Usability of intravenous thiamine injection test compared with odor stick identification test for Japanese patients with severe traumatic brain injury.

OBJECTIVE: Olfactory dysfunction is often observed after severe traumatic brain injury (sTBI). Its diagnosis is difficult because patients with sTBI have a communication disability following impaired consciousness and communication disorder. The intravenous thiamine injection (IT) test is one of the representative diagnostic examinations to identify dysfunction, and it is often used in medical certification for liability insurance of automobiles in Japan because it could be judged by a simple reaction. However, the extent of usefulness of the IT test in the diagnosis of olfactory dysfunction in patients with sTBI is unknown. In this study, we validated the usability of the IT test and compared the results with those of the odor stick identification test for the Japanese (OSIT-J) to evaluate the sensitivity of the IT test in patients with sTBI. METHODS: The study enrolled 205 subjects, including 10 healthy volunteers and 195 patients with sTBI. First, we examined olfactory dysfunction in sTBI patients using OSIT-J. Subsequently, we performed the IT test among patients with olfactory dysfunction. RESULTS: In the first part, 41 subjects, including 10 healthy volunteers, were examined by using the OSIT-J test. As a result, 28 patients were diagnosed with olfactory dysfunction (90.3%, p<0.0001), including anosmia and parosmia, compared with healthy volunteers. Among the 12 odors, garlic odor was easily recognized for patients with olfactory dysfunction. As a consequence of the IT test for 11 patients with olfactory dysfunction, four patients recognized thiamine odor, and seven patients did not. All four patients could recognize the garlic odor of OSIT-J, but 2 of the seven patients could recognize the garlic odor of OSIT-J, suggesting that the thiamine odor is linked to garlic odor (p=0.046), but not always. The detection rate of olfactory dysfunction through the IT test was 36.4%. CONCLUSION: Our data showed that garlic odor, which is similar to thiamine odor, was easily recognizable for patients with sTBI. However, the IT test might overlook the diagnosis of olfactory dysfunction because it only identifies one odor. In addition, thiamine frequently induces angialgia. We should pay attention to the overconfidence of the IT test for patients with sTBI.

Multidisciplinary attentive treatment for patients with chronic disorders of consciousness following severe traumatic brain injury in the NASVA of Japan.

Primary Objective: The aim of this study was to demonstrate the clinical outcomes of long-term multidisciplinary attentive treatment (MAT) in patients with chronic disorders of consciousness (DOC) due to severe traumatic brain injury (TBI) following automotive accidents.Research Design: Five hundred and ten patients (mean age: 40.4 years) were enrolled in this retrospective study.Methods and Procedures: Patients were provided MAT for one to several years in the eight medical facilities of the National Agency for Automotive Safety and Victims' Aid (NASVA) in Japan. Clinical status for consciousness, communication, and activities of daily living were evaluated using the NASVA grading system.Outcomes and results: Following MAT, NASVA scores at discharge were significantly improved compared to those at admission in every patient subgroup including sex, age, NASVA score, and association with/without hypoxic encephalopathy at admission. Younger age, shorter interval between injury and admission, and better neurocognitive function at admission were found to be significant and independent factors for a good prognosis.Conclusions: MAT can partially improve the cognitive and physical abilities of patients with chronic DOC. From the perspective of not only restoring a patient's daily life, but also reducing the caregiver's burden, this type of treatment program warrants more public attention.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury.

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient's condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

Increased brain glucose metabolism in chronic severe traumatic brain injury as determined by longitudinal 18F-FDG PET/CT.

Little is known about changes in glucose metabolism in patients with chronic severe traumatic brain injury (sTBI). It remains to be elucidated how neurological manifestations of sTBI are associated with brain glucose metabolism during longitudinal follow-up. We show here that neurological manifestations are associated with changes of brain glucose metabolism by using two serial 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images. In this longitudinal observational study, two serial 18F-FDG PET/CT images from each of 45 patients were analyzed for whole-brain maximum standardized uptake values (SUVmax). For clinical assessment, we applied two different scales: the coma recovery scale-revised and the original Chiba score with additional information regarding nutrition, excretion, facial expression, and position change of the patient's relative immobility and bedridden state. As a result, the increased FDG uptake group was associated with a high level of wakefulness (first PET, p = 0.04; second PET, p = 0.01) and small ventricular size (first PET, p = 0.01; second PET, p = 0.01). In addition, anticonvulsant withdrawal (p = 0.001), improvement of total Chiba score (p = 0.01), language expression (p = 0.03), position change (p = 0.03), and communication (p = 0.03) were accelerated in the increased FDG uptake group. Spearman's rank correlation coefficients of change in SUVmax and language expression between the first and second PET were 0.4 (p = 0.01). Our results indicate that chronic severe traumatic head injury patients have changed brain glucose metabolism.

Association between uncooperativeness and the glucose metabolism of patients with chronic behavioral disorders after severe traumatic brain injury: a cross-sectional retrospective study.

BAKGROUND: Patients with behavioral disorders following severe traumatic brain injury (sTBI) often have disorders of consciousness that make expressing their emotional distress difficult. However, no standard method for assessing the unsettled and unforeseen responses that are associated with behavioral disorders has yet to be established. Because the thalamus is known to play a role in maintaining consciousness and cognition, we used 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) to examine the association between brain glucose metabolism in the thalamus and behavioral disorders. METHODS: We retrospectively analyzed 70 consecutive patients with sTBI who had been involved in motor vehicle accidents. To assess behavioral disorders, we evaluated 18 symptoms using the Brief Psychiatric Rating Scale (BPRS): Emotional Withdrawal, Conceptual Disorganization, Tension, Mannerisms and Posturing, Motor Retardation, Uncooperativeness, Blunted Affect, Excitement, Somatic Concern, Anxiety, Feeling of Guilt, Grandiosity, Depressive Mood, Hostility, Suspiciousness, Hallucinatory Behavior, Unusual Thought Content, and Disorientation. First, we identified clinical characteristics of sTBI patients with behavioral disorders. Next, we retrospectively analyzed 18F-FDG-PET/CT data to assess how thalamic activity was related with abnormal behaviors. RESULTS: Twenty-six patients possessed the minimum communicatory ability required for psychiatric interview. Among them, 15 patients (57.7%) were diagnosed with behavioral disorder, 14 of whom had reached a stable psychiatric state after about 426.6 days of treatment. Excitement (13 patients) and uncooperativeness (10 patients) were the most frequently observed symptoms. Available 18F-FDG-PET/CT data indicated that thalamic glucose metabolism was imbalanced and lateralized (p = 0.04) in 6 patients who exhibited uncooperativeness. CONCLUSIONS: Behavioral symptoms of excitement and uncooperativeness were common in patients with sTBI, although most symptoms improved as the chronic stage continued. Our data support the idea that imbalanced laterality of glucose metabolism in the thalamus might be related to behavioral disorders characterized by uncooperativeness. TRIAL REGISTRATION: UMIN 000029531. Registered 27 March 2017, retrospectively registered.

[Usefulness of FDG-PET for the diagnosis of copper deficiency at an early stage: a case report].

For the patients under long-term tube feeding, copper deficiency is known to be a cause of neutropenia and/or anemia. It is recognized as reversible myelodysplasia, since the condition improves by giving a copper supplementation. Myelodysplasia caused by copper deficiency is difficult to be diagnosed because it is not so common, and often it takes a long time to reach correct diagnosis. We reported usefulness of FDG-PET for the diagnosis of myelodysplasia caused by copper deficiency in early stage. The case was 46 y.o. male patient in vegetative state for 2 years after traumatic brain injury. Laboratory examination revealed slight leukopenia. PET/CT demonstrated high and diffuse FDG accumulation mainly in the vertebral bone marrow. Based on the lower levels of serum copper and ceruloprasmin, the patient was diagnosed as copper deficiency. After treatment of copper supplementation, FDG accumulation of the bone marrow disappeared, and the serum copper level has normalized. From the FDG-PET findings, even in the early stage of copper deficiency, high glucose metabolism of bone marrow was shown.

Gamma knife radiosurgery for metastatic brain tumors from lung cancer: a comparison between small cell and non-small cell carcinoma.

OBJECT: The purpose of this retrospective study was to evaluate the effectiveness of gamma knife radiosurgery (GKS) for the treatment of metastatic brain tumors from lung cancer, with particular reference to small cell lung carcinoma (SCLC) compared with non-SCLC (NSCLC). METHODS: Two hundred forty-five consecutive patients meeting the following five criteria were evaluated in this study: 1) no prior brain tumor treatment; 2) 25 or fewer lesions; 3) a maximum of three tumors with a diameter of 20 mm or larger; 4) no surgically inaccessible tumor 30 mm or greater in diameter; and 5) more than 3 months of life expectancy. According to the same treatment protocol, large tumors (> or = 30 mm) were surgically removed and the other small lesions (< 30 mm) were treated with GKS. New lesions were treated with repeated GKS. Chemotherapy was administered, according to the primary physician's protocol, as aggressively as possible. Progression-free, overall, neurological, qualitative, and new lesion-free survival were calculated with the Kaplan-Meier method and were compared in the SCLC and NSCLC groups by using the log-rank test. The poor prognostic factors for each type of survival were also analyzed with the Cox proportional hazard model. CONCLUSIONS: Tumor control rate at 1 year was 94.5% in the SCLC group and 98% in the NSCLC group. The median survival time was 9.1 months in the SCLC group and 8.6 months in the NSCLC group. The 1-year survival rates in the SCLC group were 86.5% for neurological survival and 68.9% for qualitative survival; those in the NSCLC group were 87.9% for neurological and 78.9% for qualitative survival. The estimated median interval to emergence of a new lesion was 6.9 months in the SCLC group and 9.8 months in the NSCLC group. There was no significant difference between the two groups for any type of survival; this finding was verified by multivariate analysis. The results of this study suggest that GKS appears to be as effective in treating brain metastases from SCLC as for those from NSCLC.