Tomoyuki Maruo

Testing of semichronically implanted retinal prosthesis by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa.

PURPOSE To examine the safety and effectiveness of a retinal prosthesis that is implanted semichronically in two patients with advanced retinitis pigmentosa (RP). METHODS Two eyes of two patients with advanced RP had a retinal prosthesis implanted in a sclera pocket of one eye. The visual acuity of both eyes before the implantation was bare light perception. Phosphenes were elicited by suprachoroidal-transretinal stimulation (STS). The internal devices of the STS were implanted under the skin on the temporal side of the head, and the 49 electrode-array was implanted in the scleral pocket of one eye. Biphasic electrical pulses (duration, 0.5 ms; frequency, 20 Hz) were delivered through nine active electrodes. The threshold current was determined by currents ≤1 mA. Behavioral tasks were used to determine the functioning of the prosthesis. RESULTS The surgery was completed without a retinal detachment and retinal/vitreous hemorrhage. The implanted STS system remained functional for the 4-week test period. Phosphenes were elicited by currents delivered through six electrodes in Patient 1 and through four electrodes in Patient 2. The success of discriminating two bars was better than the chance level in both patients. In Patient 2, the success of a grasping task was better than the chance level, and the success rate of identifying a white bar on a touch panel increased with repeated testing. CONCLUSIONS Semichronic implantation of a microelectrode-STS system showed that it was safe and remained functional for at least 4 weeks in two patients with advanced RP. (www.umin.ac.jp/ctr number, R000002690.).

Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease

Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinsons disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% ± 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms.

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.

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease.

&NA; Patients with Parkinson’s disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN‐DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN‐DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold‐induced and heat‐induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS‐on mode when compared with the DBS‐off mode (P < .001), whereas the CSTs and WSTs of patients in the DBS‐off mode were significantly greater than those of healthy control subjects (P < .02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P < .02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN‐DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease‐related brain network abnormalities. Quantitative evaluation on the effect of deep brain stimulation of the subthalamic nucleus on temperature sensation and pain suggested that it could improve impaired temperature sensation in patients with Parkinson’s disease.

Chronic Implantation of Newly Developed Suprachoroidal-Transretinal Stimulation Prosthesis in Dogs

PURPOSE To investigate the feasibility of implanting a newly developed suprachoroidal-transretinal stimulation (STS) prosthesis in dogs and to determine its biocompatibility and stability over a 3-month period. METHODS The STS prosthesis system consisted of an array of 49 electrodes (nine were active), an intravitreal return electrode, and an extraocular microstimulator. The 49-electrode array was implanted into a scleral pocket of each of three healthy beagle dogs. Color fundus photography, fluorescein angiography, electroretinography, and functional testing of the STS system were performed postoperatively. The dogs were euthanatized 3 months after the implantation, and the retinas were evaluated histologically. RESULTS All the prostheses were successfully implanted without complications, and no serious complications occurred during the 3-month postoperative period. The fixation of the implant was stable throughout the experimental period. Fluorescein angiography showed that the entire retina, including the area on the electrode array, remained well perfused without intraocular inflammation. Electroretinograms recorded from the eyes with the prosthesis did not differ significantly from those recorded from control eyes. Functional testing of the STS system showed that this system performed well for the 3-month experimental period. Histologic evaluations showed good preservation of the retina over the electrode array. CONCLUSIONS Implantation of a newly developed STS retinal prosthesis into a scleral pocket of beagle dogs is surgically feasible and can be performed without significant damage to the retina or the animal. The biocompatibility and stability of the system were good for the 3-month observation period.

Cortical excitability changes after high-frequency repetitive transcranial magnetic stimulation for central poststroke pain.

&NA; Repetitive transcranial magnetic stimulation of the primary motor cortex restored the abnormal intracortical facilitation in patients with central poststroke pain. &NA; Central poststroke pain (CPSP) is one of the most refractory chronic pain syndromes. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been demonstrated to provide moderate pain relief for CPSP. However, the mechanism underlying the pain relief remains unclear. The objective of this study was to assess changes in cortical excitability in patients with intractable CPSP before and after rTMS of the primary motor cortex. Subjects were 21 patients with CPSP of the hand who underwent rTMS. The resting motor threshold, the amplitude of the motor evoked potential, duration of the cortical silent period, short interval intracortical inhibition, and intracortical facilitation were measured as parameters of cortical excitability before and after navigation‐guided 5 Hz rTMS of the primary motor cortex corresponding to the painful hand. Pain reduction from rTMS was assessed with a visual analog scale. The same parameters were measured in both hemispheres of 8 healthy controls. Eight of 21 patients experienced ≥30% pain reduction after rTMS (responders). The resting motor threshold in the patients was higher than those in the controls at baseline (P = .035). Intracortical facilitation in the responders was lower than in the controls and the nonresponders at baseline (P = .035 and P = .019), and significantly increased after rTMS (P = .039). There were no significant differences or changes in the other parameters. Our findings suggest that restoration of abnormal cortical excitability might be one of the mechanisms underlying pain relief as a result of rTMS in CPSP.

Validity, Reliability, and Assessment Sensitivity of the Japanese Version of the Short-Form McGill Pain Questionnaire 2 in Japanese Patients with Neuropathic and Non-Neuropathic Pain

OBJECTIVE The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). DESIGN This is a cross-sectional study. PATIENTS AND METHODS The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbachs α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. RESULTS The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. CONCLUSION These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain.

Daily Repetitive Transcranial Magnetic Stimulation for Poststroke Upper Limb Paresis in the Subacute Period

BACKGROUND We conducted a randomized, double-blind, sham-controlled study to assess the efficacy in motor recovery and safety of daily repetitive transcranial magnetic stimulation (rTMS) in subacute stroke patients. METHODS Forty-one patients were randomly assigned to a real or sham stimulation group. Each patient underwent regular rehabilitation accompanied by a series of 10 daily 5-Hz rTMS of the ipsilesional primary motor cortex (M1) or sham stimulation. The primary outcome was motor recovery evaluated by the Brunnstrom stages (BS). The secondary outcomes were improvement in the Fugl-Meyer Assessment (FMA), grip power, National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), a quantitative measurement of finger tapping movement, and the incidence of adverse events. RESULTS Thirty-nine patients completed the study and were included in the analyses. The real rTMS group demonstrated additional improvement in the BS hand score at the last follow-up compared to the sham. The grip power, the NIHSS motor score, and the number of finger taps in the affected hand improved in the real stimulation group but not in the sham group. The BS upper limb scores, the FMA distal upper limb score, the NIHSS total score, and the FIM motor score showed improvement from baseline at the earlier time points after the real rTMS. There were no additional improvements in the other scores after the real rTMS compared to the sham. No serious adverse events were observed. CONCLUSIONS Our results suggest that dailyhigh-frequency rTMS of the ipsilesional M1 is tolerable and modestly facilitates motor recovery in the paralytic hand of subacute stroke patients.

Eccentric Figure-Eight Coils for Transcranial Magnetic Stimulation

Previously we proposed an eccentric figure-eight coil that can cause threshold stimulation in the brain at lower driving currents. In this study, we performed numerical simulations and magnetic stimulations to healthy subjects for evaluating the advantages of the eccentric coil. The simulations were performed using a simplified spherical brain model and a realistic human brain model. We found that the eccentric coil required a driving current intensity of approximately 18% less than that required by the concentric coil to cause comparable eddy current densities within the brain. The eddy current localization of the eccentric coil was slightly higher than that of the concentric coil. A prototype eccentric coil was designed and fabricated. Instead of winding a wire around a bobbin, we cut eccentric-spiral slits on the insulator cases, and a wire was woven through the slits. The coils were used to deliver magnetic stimulation to healthy subjects; among our results, we found that the current slew rate corresponding to motor threshold values for the concentric and eccentric coils were 86 and 78 A/µs, respectively. The results indicate that the eccentric coil consistently requires a lower driving current to reach the motor threshold than the concentric coil. Future development of compact magnetic stimulators will enable the treatment of some intractable neurological diseases at home.

Validation of the Japanese version of the pain self-efficacy questionnaire in Japanese patients with chronic pain.

OBJECTIVES The present study aimed to develop the Japanese version of the Pain Self-Efficacy Questionnaire (PSEQ-J) and to evaluate its psychometric properties. DESIGN Cross-sectional design. SETTING A pain clinic, a neurosurgery unit, and an orthopedic surgery unit in one university hospital and a pain clinic in a municipal hospital. METHODS One hundred and seventy-six participants completed study measures, which included 1) the PSEQ-J, 2) the Hospital Anxiety and Depression Scale, 3) the Pain Catastrophizing Scale, 4) the Medical Outcome Study Short-Form 36, 5) the Pain Disability Assessment Scale, and 6) the Short-Form McGill Pain Questionnaire. RESULTS The PSEQ-J demonstrated adequate reliability and validity. Hierarchical multiple regression analyses showed that pain self-efficacy as measured with the PSEQ-J accounted for a significant proportion of the variance on the measures administered in the present study. The PSEQ-J was most strongly associated with social activity. CONCLUSIONS The results demonstrated that the PSEQ-J has adequate psychometric properties, supporting its use in clinical and research settings and suggest that the PSEQ-J may be particularly strongly associated with more social and less physical activity.