Aiki Marushima

Newly Synthesized Radical-Containing Nanoparticles Enhance Neuroprotection After Cerebral Ischemia-Reperfusion Injury

BACKGROUND:Antioxidant nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) have been investigated for their ability to scavenge free radicals produced by ischemia-reperfusion injury. However, the short in vivo half-life and toxicity of TEMPO have limited their clinical application. OBJECTIVE:We developed a core-shell-type nanoparticle, termed a radical-containing nanoparticle (RNP), to deliver nitroxyl radicals with prolonged in vivo half-life and pH-sensitivity. We evaluated the ability of RNP to deliver TEMPO radicals to the ischemic brain and scavenge free radicals in cerebral ischemia-reperfusion injury using rats. METHODS:When RNPs were administrated to middle cerebral artery occlusion rats, the delivery and clearance of RNPs were detected using electron paramagnetic resonance (EPR) assay. The production of superoxide anion in neuronal cells was observed with dihydroethidium staining. The treatment effects were evaluated by measuring the cerebral infarction volumes, lipid peroxidation and protein oxidation, and neurological symptom scoring. RESULTS:The TEMPO radicals contained in RNPs were detected for 6 hours after intravenous administration as a triplet EPR signal in the ischemic brain, and RNPs significantly reduced the production of superoxide anion in neuronal cells compared with saline and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyls (TEMPOL). The infarction volumes of rats treated by RNPs were significantly lower than those of rats treated by saline, micelles, and TEMPOL. In addition, RNP treatment suppressed lipid peroxidation and protein oxidation, and limited the adverse effects of TEMPO radicals such as hypotension. CONCLUSION:RNPs could be a promising neuroprotective agent with their enhanced ability to scavenge free radicals and reduced toxicity.

Intracranial dural arteriovenous fistula showing diffuse MR enhancement of the spinal cord: case report and review of the literature.

BACKGROUND Cervical myelopathy resulting from intracranial dural arteriovenous fistula (AVF) is uncommon. Knowledge of the magnetic resonance imaging (MRI) appearance of such lesions is important because many patients with myelopathy are initially examined by MRI, and an incorrect diagnosis could result in delayed or improper treatment. We describe a rare case of myelopathy due to an intracranial dural AVF showing diffuse enhancement of the cervical spinal cord. CASE DESCRIPTION A 64-year-old male presented with progressive myelopathy and respiratory insufficiency. Cerebral angiography disclosed an AVF at the craniocervical junction draining intrathecally into the spinal medullary veins. MRI revealed dilated perimedullary vessels around the craniocervical junction, as well as spinal cord swelling with high signal intensity changes. Diffuse intense enhancement of the cervical spinal cord was also seen on postcontrast images. Embolization via the afferent artery was successfully performed, and the fistula was then microsurgically obliterated via a lateral suboccipital approach. This procedure arrested a rapidly progressive myelopathy. CONCLUSION Intracranial dural AVF showing diffuse enhancement of the spinal cord is extremely rare, and this enhancement effect may indicate pathologic changes of the spinal cord. MRI only is not useful for diagnosis, but also for demonstrating pathologic changes and predicting the outcomes of patients with intracranial dural AVF.

Enhanced bone formation using hydroxyapatite ceramic coated with fibroblast growth factor-2

Our objective was to develop a bone substitute coated with fibroblast growth factor-2 (FGF-2) that subsequently releases FGF-2. We investigated the use of our system of bone substitutes to induce bone formation. Hydroxyapatite ceramic buttons (HAP-CBs) were coated with FGF-2 by precipitation in supersaturated calcium phosphate solution. HAP-CBs were coated with high or low doses of FGF-2, denoted as FGF-H and FGF-L. The release of FGF-2 from FGF-H and FGF-L was evaluated using its release profile and bioactivity. The efficacy of the subsequent bone formation was quantified using rats with round-shaped bone defects (5mm in diameter) of the right parietal bone. Group 1 was treated only with HAP-CBs, group 2 with HAP-CBs and drops of FGF-2 solution, group 3 with FGF-L and group 4 with FGF-H. To detect the release of FGF-2 in vivo, the expression of bone morphogenic protein-2 (BMP-2) was measured in the defective bone tissue. FGF-2 was released in vitro from FGF-H and FGF-L, and maintained its bioactivity. Rats treated with FGF-L showed better bone formation than rats from the other groups. BMP-2 expression was detected in the defective bone tissues of group 3 at 14 days, which might indicate in vivo FGF-2 release during this period. A specific FGF-2 concentration may be needed for bone formation, and our system can release FGF-2 at adequate concentrations to induce bone formation.

Subarachnoid hemorrhage not due to ruptured aneurysm in moyamoya disease.

A patient with moyamoya disease presenting with subarachnoid hemorrhage (SAH) is reported. A 38-year-old Japanese woman developed a sudden onset headache and nausea during hospitalization for a cerebral infarct in the right frontal lobe. CT scan showed SAH in the left frontal sulci. Cerebral angiogram showed stenosis of the distal bilateral internal carotid arteries with moyamoya vessels, and significant transdural anastamoses from the left external carotid artery to cortical arteries on the left frontal cortex. The patient was kept normotensive and underwent a right-sided surgical revascularization procedure, remaining well for three years. SAH not due to ruptured aneurysm in moyamoya disease is rare. The cause of the SAH was thought to be disruption of the transdural anastomotic vessels. Recognition of these fragile vessels in moyamoya disease is essential.

Selective arterial embolization with n-butyl cyanoacrylate in the treatment of aneursymal bone cyst of the thoracic vertebra: a case report.

Study Design. A case report of aneurysmal bone cyst of the mobile spine. Objective. To present a pediatric case of aneurysmal bone cyst (ABC) of the mobile spine treated successfully by selective arterial embolization (SAE) with n-butyl cyanoacrylate (NBCA). Summary of Background Data. The endovascular treatment is an important treatment option for the ABC of the mobile spine. However, there are few reported case treated by SAE with NBCA. Methods. A 12-year-old healthy boy was introduced with a complaint of back pain. Computed tomography showed an osteolytic expanding mass in the pedicle, lamina, and spinous process on the level of T10. Magnetic resonance imaging revealed a multicystic mass with fluid-fluid levels that extended into the spinal canal and compressed the spinal cord from the dorsal side. Digital subtraction angiography showed an abnormal blood supply from the posterior spinal branch of the left T9 artery. An abnormal mass was diagnosed as an ABC based on these neuroradiologic examinations. Result. The patient underwent SAE with NBCA (Histoacryl, B. Braun, Melsungen, Germany) diluted with Lipiodol (Laboratorie Guerbet, France) in a rate of 1:4. Computed tomography performed 1 month after treatment revealed partial ossification of the bone cortex. MR imaging showed shrinkage of the cyst and decompression of the spinal cord. Back pain of the patient disappeared and the shrunken cyst was stable without recurrence during the 3-year follow-up period. Conclusion. SAE in a pediatric case with ABC of the mobile spine was effective in improving of clinical symptom and shrinking of the cyst.

The voluntary driven exoskeleton Hybrid Assistive Limb (HAL) for postoperative training of thoracic ossification of the posterior longitudinal ligament: a case report

Context: The hybrid assistive limb (HAL) is a wearable robot suit that assists in voluntary control of knee and hip joint motion by detecting bioelectric signals on the surface of the skin with high sensitivity. HAL has been reported to be effective for functional recovery in motor impairments. However, few reports have revealed the utility of HAL for patients who have undergone surgery for thoracic ossification of the posterior longitudinal ligament (thoracic OPLL). Herein, we present a postoperative thoracic OPLL patient who showed remarkable functional recovery after training with HAL. Findings: A 63-year-old woman, who could not walk due to muscle weakness before surgery, underwent posterior decompression and fusion. Paralysis was re-aggravated after the initial postoperative rising. We diagnosed that paralysis was due to residual compression from the anterior lesion and microinstability after posterior fixation, and prescribed bed rest for a further 3 weeks. The incomplete paralysis gradually recovered, and walking training with HAL was started on postoperative day 44 in addition to standard physical therapy. The patient underwent 10 sessions of HAL training until discharge on postoperative day 73. Results of a 10-m walk test were assessed after every session, and the patients speed and cadence markedly improved. At discharge, the patient could walk with 2 crutches and no assistance. Furthermore, no adverse events associated with HAL training occurred. Conclusion: HAL training for postoperative thoracic OPLL patients may enhance improvement in walking ability, even if severe impairment of ambulation and muscle weakness exist preoperatively.

Gait training of subacute stroke patients using a hybrid assistive limb: a pilot study

Abstract Purpose To determine whether gait training with a hybrid assistive limb (HAL) as an exoskeleton robotic device was safe and could increase functional mobility and gait ability in subacute stroke patients. Methods The participants were eight patients with post-stroke hemiparesis whose walking impairment and gait recovery curves had plateaued. The intervention program was gait training using HAL and a walker for 20 min daily 5 days a week for 5 weeks. The 10-m maximum walking speed (MWS), self-selected walking speed (SWS) and 2-min-walk test (2MT) without HAL were used as primary outcome measures to determine the effects of training. The Berg Balance Scale (BBS), Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA) and functional ambulation category (FAC) were assessed as secondary outcomes. These measures were assessed before and after the 5-week intervention program and were analyzed statistically using a paired t-test. Results All eight participants completed the intervention program with no adverse events. There were significant increases in MWS, SWS and 2MT. BBS, FMA and FAC also increased, but not significantly. Conclusion The new HAL exoskeleton robotic device was efficient and safe for improving motor function and gait in patients in the subacute stage after stroke. Implications for Rehabilitation Gait training using HAL will improve gait ability of individuals with post stroke. The HAL achieve intensive gait training without increase spasticity and abnormal gait pattern.

Elevated diffusion anisotropy in gray matter and the degree of brain compression

OBJECT For several decades, clinicians have predicted intraparenchymal brain pressure or brain tissue compression indirectly based on the degree of distortion of the midline structures (midline shift) and ventricle wall (ventriculomegaly) observed on conventional MRI. However, this method has several limitations. Diffusion tensor imaging (DTI) is a novel MRI technique that can provide information about the microstructural properties of compressed tissue. In this study, the authors evaluated whether DTI can precisely define the degree of tissue compression in patients with chronic subdural hematoma (CSDH). METHODS The study sample consisted of 18 patients (mean age 71 years, 10 men and 8 women) with unilateral CSDH and 12 age-matched volunteers. Diffusion tensor imaging results were acquired before and after the surgical irrigation in the CSDH group. Subdural pressure during the operation was also measured. Fractional anisotropy (FA) values were evaluated at several locations, including the gray matter. RESULTS The FA values of the gray matter, especially in the caudate nucleus and putamen, were increased in the patients with CSDH compared with the control group. The change in FA data before and after surgery (ΔFA) correlated with the degree of tissue compression evaluated by measurement of the subdural pressure. Furthermore, the increased FA values in patients with CSDH decreased after surgery. CONCLUSIONS These findings indicate that FA values of the gray matter, especially in the caudate nucleus and putamen, may be important markers of tissue compression. The assessment of FA values of the gray matter will result in a new, less-invasive diagnostic technique to evaluate the degree of brain compression.

Decrease of spasticity after hybrid assistive limb® training for a patient with C4 quadriplegia due to chronic SCI

Context: Recently, locomotor training with robotic assistance has been found effective in treating spinal cord injury (SCI). Our case report examined locomotor training using the robotic suit hybrid assistive limb (HAL) in a patient with complete C4 quadriplegia due to chronic SCI. This is the first report examining HAL in complete C4 quadriplegia. Findings: The patient was a 19-year-old man who dislocated C3/4 during judo 4 years previously. Following the injury, he underwent C3/4 posterior spinal fusion but remained paralyzed despite rehabilitation. There was muscle atrophy under C5 level and no sensation around the anus, but partial sensation of pressure remained in the limbs. The American Spinal Injury Association impairment scale was Grade A (complete motor C4 lesion). HAL training was administered in 10 sessions (twice per week). The training sessions consisted of treadmill walking with HAL. For safety, 2 physicians and 1 therapist supported the subject for balance and weight-bearing. The devices cybernic autonomous control mode provides autonomic physical support based on predefined walking patterns. We evaluated the adverse events, walking time and distance, and the difference in muscle spasticity before and after HAL-training using a modified Ashworth scale (mAs). No adverse events were observed that required discontinuation of rehabilitation. Walking distance and time increased from 25.2 meters/7.6 minutes to 148.3 meter/15 minutes. The mAs score decreased after HAL training. Conclusion: Our case report indicates that HAL training is feasible and effective for complete C4 quadriplegia in chronic SCI.

Time-Course Analysis of Brain Perfusion Single Photon Emission Computed Tomography Using a Three-Dimensional Stereotactic Region-of-Interest Template in Patients with Moyamoya Disease

OBJECTIVE To verify the usefulness of the time-course analysis of regional cerebral blood flow (CBF) and cerebrovascular reserve (CVR) estimated quantitatively using the three-dimensional stereotactic region-of-interest template (3DSRT) to assess clinical status in patients with moyamoya disease. METHODS The study comprised 12 patients (5 men and 7 women, age 35.1 years ± 14.7), with 21 hemispheres with the diagnosis of moyamoya disease. During the period 2005-2009, the patients underwent initial and follow-up technetium-99m ethyl cysteinate dimer (Tc-99m ECD) single photon emission computed tomography (SPECT). The 3DSRT was applied to estimate regional CBF at rest and CVR. Time-course changes in CBF and CVR in a region of the middle cerebral artery were analyzed, considering the presence or absence of an ischemic event and revascularization surgery. RESULTS CBF in hemispheres with ischemic events was significantly lower than CBF in hemispheres without ischemic events based on the initial SPECT study (P = 0.001). In 15 hemispheres with a hemodynamic disorder, CBF of the hemispheres in which revascularization was performed was increased significantly after surgery (P = 0.01). In contrast, the follow-up CVR of the hemispheres in which revascularization was not performed was decreased significantly compared with the CVR determined in the initial SPECT study (P = 0.0008). CONCLUSIONS Time-course analysis and quantitative SPECT using the 3DSRT were useful for the evaluation of hemodynamic changes involved in disease progression and revascularization surgery in patients with moyamoya disease. Regular hemodynamic studies are important for patients with hemodynamic disorders to determine whether revascularization surgery is indicated to reduce the risk of future stroke.