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.

The role of optimal cut-off diagnosis in 11C-methionine PET for differentiation of intracranial brain tumor from non-neoplastic lesions before treatment.

PURPOSE: Amino acid positron emission tomography (PET) may provide additional information to computed tomography and magnetic resonance imaging for detecting the pretreatment diagnosis of intracranial lesions. The purpose of this study was to investigate the role of cutoff values of 11C-METPET, an amino acid PET tracer, in the differentiation of pretreatment brain tumors from non-neoplastic lesions. METHODS: This retrospective cohort study analyzed 101 pretreatment patients with a definitive diagnosis out of a total of 425 consecutive 11C-METPET imaging studies. The standardized uptake values (SUV) and the ratios of lesion to contralateral normal frontal-lobe gray matter uptake (L/N ratios) were measured. Cutoff values for the differential diagnosis of brain tumors from non-neoplastic lesions were determined using receiver operating characteristics curve (ROC) analysis. RESULTS: Based on the ROC analyses, the cutoffs were 3.33 for maximum SUV, 2.54 for mean SUV, 2.33 for peak SUV, 2.04 for Lmax/Nmean, and 2.23 for Lmax/Nmax. The sensitivity and specificity of these cutoffs were 69.2% and 82.6%, respectively, for maximum SUV, 64.1% and 91.3% for mean SUV, 69.2% and 91.3% for peak SUV, 70.5% and 91.3% for Lmax/Nmax and 75.6% and 82.6% for Lmax/Nmean. CONCLUSION: In differentiating intracranial brain tumor from non-neoplastic lesion with 11C-METPET, the use of optimal cutoff values indicates the high specificity, which means that positive result indicates the high likelihood of brain tumor. Considering the high specificity of 11C-METPET, more invasive examinations such as biopsy may be considered in positive cases.

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.

Changes in the brain activation balance in motor-related areas after constraint-induced movement therapy; a longitudinal fMRI study.

PRIMARY OBJECTIVE: This study investigated the longitudinal changes in brain activation balance in motor-related areas after Constraint-Induced Movement Therapy (CIMT). METHODS AND PROCEDURES: The subjects included seven ischemic stroke patients with mild right hemiparesis. Eight normal subjects were also included. The patients underwent functional MRI and motor function tests (Fugl-Meyer Assessment; FMA, modified Wolf Motor Function Test; mWMFT) both before and immediately after CIMT and also after a 3-month follow-up. RESULTS: The motor function test scores improved immediately after CIMT; moreover, these scores were either maintained or improved even at the 3-month follow-up. In a comparison of the chronological data of the contralaterality index of the affected hand movement, the cerebellar activity changed significantly to ipsilateral activation immediately after CIMT and thereafter the cerebellar activity further changed to ipsilateral activation at the 3-month follow-up. A correlation was observed among the contralateral activation, FMA and mWMFT scores in SM1 and the ipsilateral activation and in the mWMFT scores in the cerebellum at the 3-month follow-up examinations. CONCLUSION: The participation of the contralateral SM1 and the ipsilateral cerebellum is thus considered to play an important role in the satisfactory recovery of the motor function after CIMT intervention.

[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.

Hyperactivity of the facial nucleus produced by chronic electrical stimulation in rats.

OBJECTIVE: There are two hypotheses for the pathogenesis of hemifacial spasm (HFS): abnormal cross-transmission between the facial nerve fibers at a site of vascular compression, and hyperactivity of the facial nucleus. To further elucidate the mechanism of HFS, we established an animal model. We applied chronic electrical stimulation (CES) to the facial nucleus in rats, and clarified functional and morphological changes in the nucleus. METHOD: Under anesthesia, a novel intracranial electrode was stereotactically implanted in the facial nucleus of six rats. CES of the facial nucleus via the implanted electrode was applied for 5 min daily for three weeks (CES animals). Facial electromyograms (EMGs) were recorded at rest and during electrical stimulation to study the excitability of the facial nucleus at 1, 2, and 4 weeks after initiating CES. As control animals, six rats were implanted with intracranial electrodes, but did not undergo CES. Electrophysiological studies of the control animals were performed using the same protocol as in the CES animals. RESULT: Spontaneous abnormal movement of the facial muscle mimicking HFS did not occur. Four weeks after starting CES, one of the six CES animals developed an abnormal EMG response with a latency of 10 ms. No control animals developed such a response. CONCLUSIONS: CES of the facial nucleus can produce an abnormal EMG response very similar to the abnormal muscle response (AMR) characteristic of HFS patients. Kindling-like hyperactivity of the facial nucleus induced by CES is the cause of the AMR, suggesting a pathogenesis of HFS.

Brain temperature in patients with chronic hydrocephalus after subarachnoid hemorrhage.

The relationships between temperature indices and clinical condition on admission or improvement after ventriculoperitoneal (VP) shunting were evaluated in patients with subarachnoid hemorrhage (SAH). Brain temperatures were measured at intervals of 1 cm from the brain surface to the lateral ventricle at shunt operation. Rectal temperature was also measured. The difference between intraventricular and rectal temperatures was correlated with age (p = 0.0486), Glasgow Coma Scale (p = 0.0129), Hunt and Hess grade (p = 0.0101), and improvement score after VP shunting (p = 0.0104). Measurement of brain temperature may predict the outcome of VP shunting in patients with SAH.

Intraoperative monitoring of cochlear nerve compound action potential in cerebellopontine angle tumour removal.

Cochlear nerve compound action potential (CNAP) provides a real-time auditory evoked potential. Because of technical difficulty, CNAP monitoring has not been popular during the removal of cerebellopontine angle (CPA) tumour. To clarify the efficiency of intraoperative CNAP monitoring, we designed an intracranial electrode for CNAP monitoring and performed the simultaneous monitoring of CNAP and auditory brainstem response (ABR) in 10 patients undergoing CPA tumour removal in an attempt to preserve hearing. ABR recordings during microsurgical tumour removal were unsatisfactory in 6 patients because of severe artifacts. Reliable CNAP recordings were obtained without artifacts in all 10 patients throughout surgery. Eight patients preserved useful hearing after tumour removal, and the CNAP amplitude reflected the postoperative hearing. The newly designed intracranial electrode enables CNAP monitoring predicting the postoperative hearing more reliably than ABR. CNAP monitoring is efficient to improve the hearing preservation rate following CPA tumour removal.

[A case of the traumatic hydrocephalus after large craniectomy for acute subdural hematoma].

Decompressive craniectomy sometimes causes neurological deficits known as 'the syndrome of the sinking skin flap' or 'the symptom of the trephined'. These disorders can be corrected with cranioplasty, but there is no consensus on appropriate treatments. We report a case of successful correction of traumatic hydrocephalus following craniotomy. A 50-year-old man was admitted to our hospital with disturbance of consciousness after a head injury. Decompressive craniectomy was performed for a right acute subdural hematoma. His consciousness recovered after the operation, but then deteriorated gradually and left hemiparesis occurred. CT scan revealed midline shift from right to left. These symptoms and CT findings were not improved after cranioplasty, but were improved with removal of the CSF from the adhered subarachnoid space. The diagnosis was traumatic hydrocephalus, and a cisternoperitoneal shunt was subsequently placed. We report this case to emphasize the necessity for study of CSF circulation, as well as the importance of examination of CBF and ICP after craniectomy.

[Intraoperative monitoring of hearing function in the removal of cerebellopontine angle tumor: auditory brainstem response and cochlear nerve compound action potential].

Intraoperative hearing monitoring may be the best approach for hearing preservation in the removal of cerebellopontine angle (CPA) tumors. We designed an intracranial electrode for a reliable and consistent recording of the cochlear nerve compound action potential (CNAP), and compared the efficiency of the CNAP and auditory brainstem response (ABR) while monitoring the CPA tumor removal. Simultaneous intraoperative monitoring of CNAP and ABR were performed in 7 patients with CPA tumors (5 acoustic neurinomas and 2 epidermoids) undergoing tumor removal aimed at hearing preservation. We designed an intracranial electrode for CNAP monitoring made of a fine malleable insulated wire with a tiny tuft of oxidized cellulose on the tip. Postoperatively, the hearing of 6 patients was preserved. Useful hearing was preserved in 5 of those. ABR recordings were unsatisfactory because of severe artifacts during the tumor removal. It was discernible only in 2 of the 7 patients. Postoperatively, useful hearing was preserved in the 2 patients with a discernible ABR during the tumor removal. Four of 5 patients with no discernible ABR during the tumor removal preserved hearing. Before the tumor removal, all patients showed a reproducible CNAP of an amplitude 20 times larger than the amplitude of ABR without artifacts. A reliable CNAP was recorded consistently throughout the tumor removal in 5 patients, in whom useful hearing was preserved postoperatively. CNAP disappeared completely during the tumor removal in 1 patient who lost hearing postoperatively. Because of severe artifacts and poor specificity, the intraoperative ABR monitoring can not predict the postoperative hearing condition. Our newly designed intracranial electrode enables consistent CNAP recording during tumor removal. CNAP reflects the effect of surgical manipulations on hearing and predicts the postoperative hearing condition. CNAP is a more efficient form of intraoperative monitoring than ABR during CPA tumor removal.