Yasuhiro Osaki

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O PET study

Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H(2)(15)O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H(2)(15)O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76.1+/-25.2 before SCS to 40.6+/-4.5 after SCS (mean+/-SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS.

Differential brain processing of audiovisual sexual stimuli in men: comparative positron emission tomography study of the initiation and maintenance of penile erection during sexual arousal.

The human male psychosexual cycle consists of four phases: excitation, plateau, orgasm, and resolution. Identification of the specific neural substrates of each phase may provide information regarding the brains pathophysiology of sexual dysfunction. We previously analyzed regional cerebral blood flow (rCBF) with H(2)15O-positron emission tomography (PET) during the excitation phase (initiation of penile erection) induced by audiovisual sexual stimuli (AVSS) and identified activation of the cerebellar vermis, the bilateral extrastriate cortex, and right orbitofrontal cortex, suggesting a role of cognition/emotion in the excitement phase. In the present study, we analyzed rCBF of the same six healthy volunteers during the plateau phase (maintenance of penile erection) induced by AVSS and compared the results with those of the excitation phase. Penile rigidity was monitored in real time with RigiScan Plus during PET scanning. Images were analyzed by statistical parametric mapping (SPM) software, and rCBF in the amygdala, hypothalamus, anterior cingulate, and insula was measured. During the plateau phase, primary subcortical activation was noted in the right ventral putamen, indicating motivational factors in the sexual response via the limbic reward circuit. A significant increase in rCBF in the left hypothalamus was also observed during the plateau phase. The right anterior cingulate and left insula were specifically activated during the excitation phase but not during the plateau phase. These results indicate a significant role of the ventral putamen and the hypothalamus in the plateau phase and confirm that paralimbic and limbic components of the human brain differentially coordinate the sexual response in a psychosexual phase-dependent manner.

Cerebral hemodynamics and metabolism in adult moyamoya disease: Comparison of angiographic collateral circulation

PurposeThe extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs).MethodsThe cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.6 years) and six age-matched normal controls (mean age, 33.3 years). The cerebrovascular reserve (CVR) after acetazolamide (ACZ) loading was also estimated using iodine-123N- isopropyl-p-iodo amphetamine single photon emission computed tomography (123I-IMP SPECT).ResultsBased on the angiographic findings, eleven cerebral hemispheres with well-developed BMV (extensive BMV hemispheres) and nine cerebral hemispheres with diminished BMV (diminished BMV hemispheres) were identified. The main routes of collateral circulation in extensive BMV hemispheres were BMVs and leptomeningeal anastomoses. On the other hand, in diminished BMV hemispheres, transdural anastomosis was predominant, and leptomeningeal anastomoses were less developed. In cortices distal to the occluded internal carotid artery, the extensive BMV hemispheres exhibited a significantly lower CBF, CMRO2, CBF/CBV, and CVR (p < 0.05) and a significantly higher CBV and OEF than in diminished BMV hemispheres and controls (p < 0.05). Except for the CBF in the white matter, the mean hemodynamic and metabolic parameters of the diminished BMV hemispheres were not significantly different from those of the controls.ConclusionThe extensive development of basal moyamoya vessels is a sign of severe hemodynamic impairment in adult patients with ischemic moyamoya disease. The results may not apply to adults with hemorrhagic onset.

Motor cortex stimulation in patients with deafferentation pain: activation of the posterior insula and thalamus

OBJECT The mechanisms underlying deafferentation pain are not well understood. Motor cortex stimulation (MCS) is useful in the treatment of this kind of chronic pain, but the detailed mechanisms underlying its effects are unknown. METHODS Six patients with intractable deafferentation pain in the left hand were included in this study. All were righthanded and had a subdural electrode placed over the right precentral gyrus. The pain was associated with brainstem injury in one patient, cervical spine injury in one patient, thalamic hemorrhage in one patient, and brachial plexus avulsion in three patients. Treatment with MCS reduced pain; visual analog scale (VAS) values for pain were 82 +/- 20 before MCS and 39 +/- 20 after MCS (mean +/- standard error). Regional cerebral blood flow (rCBF) was measured by positron emission tomography with H2(15)O before and after MCS. The obtained images were analyzed with statistical parametric mapping software (SPM99). RESULTS Significant rCBF increases were identified after MCS in the left posterior thalamus and left insula. In the early post-MCS phase, the left posterior insula and right orbitofrontal cortex showed significant rCBF increases, and the right precentral gyrus showed an rCBF decrease. In the late post-MCS phase, a significant rCBF increase was detected in the left caudal part of the anterior cingulate cortex (ACC). CONCLUSIONS These results suggest that MCS modulates the pathways from the posterior insula and orbitofrontal cortex to the posterior thalamus to upregulate the pain threshold and pathways from the posterior insula to the caudal ACC to control emotional perception. This modulation results in decreased VAS scores for deafferentation pain.

Intractable benign paroxysmal positioning vertigo: long-term follow-up and inner ear abnormality detected by three-dimensional magnetic resonance imaging.

Objective: To investigate the occurrence rate, prognosis, and inner ear abnormality in intractable benign paroxysmal positioning vertigo (BPPV). Study Design: A prospective study. Setting: Tertiary referral university hospital. Patients: Intractable BPPV was defined in case of either a persistent nystagmus or a frequent relapse each lasting more than 1 year after the initial diagnosis. Intervention: T2-weighted 3-dimensional fast imaging employing steady-state acquisition sequences of magnetic resonance imaging (MRI) were reconstructed 3-dimensionally for 13 intractable BPPV patients and 14 control volunteers. Main Outcome Measure: Transition and relapse of nystagmus were monitored. Semicircular canals were evaluated for a stenosis or filling defect (obturation). Results: Eighteen patients (4 with posterior canal type, 2 with horizontal canal type with geotropic nystagmus, and 12 with apogeotropic nystagmus) fulfilled the above criteria for intractability among 495 BPPV patients. The occurrence rate of intractable BPPV was 3.6%. Also, the rate of nystagmus transition was significantly higher in patients with geotropic nystagmus and the posterior canal type (100%) compared with those with apogeotropic nystagmus (33.3%). Of the 13 intractable BPPV patients who underwent MRI, 11 (84.6%) had a total of 23 canals with abnormal appearance (29.5%), showing a significantly higher incidence compared with controls. There was no correlation between the affected canal diagnosed by MRI and the type of nystagmus. Conclusion: The low incidence of nystagmus transition in patients with apogeotropic nystagmus suggests a difference in pathophysiology between apogeotropic nystagmus and other types of BPPV. Stenosis and filling defect (obturation) of canals on MRI, which would indicate an innate narrowing and/or an otoconial jam of the semicircular canal, may account for the intractability of BPPV.

Long-Term Angiotensin-Converting Enzyme Inhibitor Perindopril Therapy Improves Cerebral Perfusion Reserve in Patients With Previous Minor Stroke

Background and Purpose— Angiotensin-converting enzyme (ACE) inhibitor–based therapy reduces the recurrence of stroke. The present study assessed the effects of long-term ACE inhibitor therapy on cerebral circulation in patients with previous minor stroke. Methods— After a run-in period, 19 patients were randomized to ACE inhibitor therapy (n=9; 4 mg of perindopril daily; mean age, 64±8 years; mean systolic/diastolic blood pressure [BP]±SD, 133±12/77±9 mm Hg) or placebo therapy (n=10; mean age, 66±9 years; mean BP, 139±10/78±8 mm Hg). Cerebral blood flow (CBF) was measured during hypercapnia, normocapnia, and hypocapnia using a positron emission tomography with H215O at entry into the study and after 3 to 12 months. Cerebral perfusion reserve (CPR) was defined as percent CBF response to a 1 mm Hg change in arterial partial pressure of CO2 between hypercapnia and hypocapnia. Results— Systolic/diastolic BP and CBF during normocapnia showed no significant changes between entry and completion of the trial in the perindopril and placebo groups. Mean value of CPR showed a significant increase in the perindopril group (from 3.7±1.7%/mm Hg to 4.8±1.7%/mm Hg; P <0.05) but not in the placebo group (from 4.1±0.8%/mm Hg to 4.2±0.6%/mm Hg; NS). Statistical parametric mapping analysis also showed global and significant increase (P <0.01, uncorrected) in CPR in the perindopril group alone. Conclusions— Long-term ACE inhibitor–based therapy had a beneficial effect on the cerebral circulation by improving CPR in patients with previous minor stroke.

The role of CT and 18F-FDG PET in managing the neck in node-positive head and neck cancer after chemoradiotherapy

Conclusion. Patients showing a complete response on computed tomography (CT) can be spared from neck dissection. Objective. To determine whether CT or fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is superior in the evaluation of persistent nodal disease after chemoradiotherapy in patients with node-positive head and neck squamous cell carcinoma (HNSCC). Patients and methods. Study entry criteria included node-positive HNSCC treated with definitive chemoradiotherapy, a local complete response, and post-treatment CT and 18F-FDG PET studies 7 weeks after chemoradiotherapy. Forty-eight patients with 60 node-positive necks were eligible. Nodes larger than 1 cm, or with central necrosis on CT, or any visually hypermetabolic nodes on 18F-FDG PET were considered positive. Regardless of PET findings, necks with positive CT were subjected to neck dissection, whereas those with negative CT were observed without neck dissection. Results. Twenty-two necks showed positive CT, 20 and 2 of which underwent neck dissection and fine needle aspiration cytology, respectively, resulting in pathologic evidence of persistent nodal disease in 13 necks. Five of 38 necks with negative CT developed regional recurrence. Diagnostic accuracy was equivalent between CT and 18F-FDG PET. There was no difference in 3-year cause-specific survival between patients with positive and negative CT (79% and 81%, respectively).

Gamma-band desynchronization in language areas reflects syntactic process of words

The aim of this study was to verify the relation between gamma-band activity and process of function words. We recorded the neuromagnetic signals in six healthy volunteers during silent reading of verbs (verb task) and forming of the past tenses (past-tense task) and investigated the spatio-temporal distribution of event-related desynchronization (ERD) and synchronization using synthetic aperture magnetometry. In both tasks, ERDs were observed simultaneously at multiple language-related areas. The left junctional area of inferior frontal sulcus and precentral sulcus and the left supramarginal gyrus showed stronger and/or longer-lasting ERDs in past-tense task than in verb task. This result suggests that the gamma-activities reflect the syntactic process of words.

Frequency-Velocity Mismatch: A Fundamental Abnormality in Parkinsonian Gait

Gait dysfunction and falling are major sources of disability for patients with advanced Parkinsons disease (PD). It is presently thought that the fundamental defect is an inability to generate normal stride length. Our data suggest, however, that the basic problem in PD gait is an impaired ability to match step frequency to walking velocity. In this study, foot movements of PD and normal subjects were monitored with an OPTOTRAK motion-detection system while they walked on a treadmill at different velocities. PD subjects were also paced with auditory stimuli at different frequencies. PD gait was characterized by step frequencies that were faster and stride lengths that were shorter than those of normal controls. At low walking velocities, PD stepping had a reduced or absent terminal toe lift, which truncated swing phases, producing shortened steps. Auditory pacing was not able to normalize step frequency at these lower velocities. Peak forward toe velocities increased with walking velocity and PD subjects could initiate appropriate foot dynamics during initial phases of the swing. They could not control the foot appropriately in terminal phases, however. Increased treadmill velocity, which matched the natural PD step frequency, generated a second toe lift, normalizing step size. Levodopa increased the bandwidth of step frequencies, but was not as effective as increases in walking velocity in normalizing gait. We postulate that the inability to control step frequency and adjust swing phase dynamics to slower walking velocities are major causes for the gait impairment in PD.

Three-dimensional kinematics and dynamics of the foot during walking: a model of central control mechanisms

The foot is a critical interface between the body and supporting surface during walking, but there is no coherent framework on which to model the dynamics of the stance and swing phases. To establish this framework, we studied the rotational and translational dynamics of foot movement in three dimensions with a motion detection system (OPTOTRAK), while subjects walked on a treadmill. Positions, velocities, and durations were normalized to leg-length and gravity. Foot position and rotation at toe-off were closely related to walking velocity. Foot pitch at toe clearance increased with walking velocity, but the medial–lateral and vertical toe positions were unaltered. Phase–plane trajectories along the fore-aft direction, i.e., plots of toe velocity versus position, were circular during the swing phases, with radii proportional to walking velocity. Peak forward, lateral, and upward velocities were linearly related to corresponding excursions, forming main sequences. A second order model predicted the changes in toe position and velocity, and the approximately hyperbolic decrements in duration as a function of walking velocity. The model indicates that the foot is controlled in an overdamped manner during the stance phase and as a feedback-controlled undamped pendulum during the swing. The data and model suggest that the state of the foot at toe-off, set by walking velocity during the stance phase, determines the dynamics of the swing phase. Thus, in addition to determining locomotion kinematics, walking velocity plays a critical role in determining the phase–plane trajectories and main sequence relationships of foot movements during the swing phases.