Tyrosine Kinase Inhibitor-induced Cerebrovascular Occlusion Presenting with Moyamoya Disease-like Stenosis of the Circle of Willis.

Vascular occlusive events are notable adverse effects of tyrosine kinase inhibitors (TKIs), which are promising treatments for chronic myeloid leukemia (CML). We herein report the case of a patient with CML who developed cerebrovascular occlusion of the circle of Willis during TKI treatment. Our patient did not meet the diagnostic criteria for moyamoya disease due to the insignificant development of moyamoya vessels. The lack of moyamoya vessel development may be explained by the suppression of tyrosine kinases that are responsible for angiogenesis. Cerebrovascular occlusion of the circle of Willis, without significant development of moyamoya vessels, may be an important phenotype of TKI-associated vasculopathy.

Stimulation of Pro-inflammatory Cytokines in Mixed Cultures of Peripheral Blood Mononuclear Cells and Anaerobic Bacteria.

In the last couple of decades, much progress has been made in studying bacteria living in humans. However, there is much more to learn about bacteria immune cell interactions. Here, we show that anaerobic bacteria do not grow when cultured overnight with human cells under atmospheric air. Air contains about 18% oxygen, which inhibits the growth of these bacteria while supporting the cultivation of human cells. The bacteria cultured with human peripheral blood mononuclear cells (PBMCs) inflamed with phytohemagglutinin (PHA) greatly increased the production of proinflammatory cytokines like tumor necrosis factor-alpha (TNFα) while inhibiting the production of monocyte chemoattractant protein-1 (MCP-1), an important chemokine.

A Fully Implantable Wireless ECoG 128-Channel Recording Device for Human Brain-Machine Interfaces: W-HERBS.

Brain-machine interfaces (BMIs) are promising devices that can be used as neuroprostheses by severely disabled individuals. Brain surface electroencephalograms (electrocorticograms, ECoGs) can provide input signals that can then be decoded to enable communication with others and to control intelligent prostheses and home electronics. However, conventional systems use wired ECoG recordings. Therefore, the development of wireless systems for clinical ECoG BMIs is a major goal in the field. We developed a fully implantable ECoG signal recording device for human ECoG BMI, i.e., a wireless human ECoG-based real-time BMI system (W-HERBS). In this system, three-dimensional (3D) high-density subdural multiple electrodes are fitted to the brain surface and ECoG measurement units record 128-channel (ch) ECoG signals at a sampling rate of 1 kHz. The units transfer data to the data and power management unit implanted subcutaneously in the abdomen through a subcutaneous stretchable spiral cable. The data and power management unit then communicates with a workstation outside the body and wirelessly receives 400 mW of power from an external wireless transmitter. The workstation records and analyzes the received data in the frequency domain and controls external devices based on analyses. We investigated the performance of the proposed system. We were able to use W-HERBS to detect sine waves with a 4.8-µV amplitude and a 60-200-Hz bandwidth from the ECoG BMIs. W-HERBS is the first fully implantable ECoG-based BMI system with more than 100 ch. It is capable of recording 128-ch subdural ECoG signals with sufficient input-referred noise (3 µVrms) and with an acceptable time delay (250 ms). The system contributes to the clinical application of high-performance BMIs and to experimental brain research.

The optimal stimulation site for high-frequency repetitive transcranial magnetic stimulation in Parkinson's disease: A double-blind crossover pilot study.

Many reports have shown improvements in motor symptoms after repetitive transcranial magnetic stimulation (rTMS). However, the best stimulation area in the brain has not currently been determined. We assessed the effects of high-frequency rTMS (HF-rTMS) on the motor and mood disturbances in Parkinson's disease (PD) patients and attempted to determine whether the primary motor area (M1), the supplementary motor area (SMA), and the dorsolateral prefrontal cortex (DLPFC) were the best treatment targets. In this randomized, double-blind crossover design study, we investigated the efficacy of 3 consecutive days of HF-rTMS over the M1, SMA, and DLPFC and compared these HF-rTMS to sham stimulations. We used motor and non-motor scales to evaluate the parkinsonian symptoms. The changes in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) scores after the application of HF-rTMS over the M1 and SMA were significantly greater than those after the sham stimulation. However, after the application of HF-rTMS over the DLPFC, the UPDRS-III scores were similar to those after the sham stimulation. No significant improvements were demonstrated in the mood disturbances after the stimulations over any of the targets. In conclusion, the application of HF-rTMS over the M1 and SMA significantly improved the motor symptoms in the PD patients but did not alter the mood disturbances.

High Titer of Acquired Factor V Inhibitor Presenting with a Pseudo-deficiency of Multiple Coagulation Factors.

Acquired coagulation factor inhibitor is a rare coagulation disorder. We herein report a patient with acquired factor V inhibitor showing a decrease in multiple coagulation factor activities. A high titer of factor V inhibitor presumably led to a marked inhibition of factor V activity in the specific factor-deficient plasma used in coagulation factor activity assays based on either an activated partial thromboplastin time (APTT) or prothrombin time (PT) clotting assay, resulting in false low values of the coagulation activity. We re-examined the coagulation factor activity using several dilutions of the patient's plasma and confirmed that the high factor V inhibitor titer had caused an apparent decrease in multiple coagulation factor activities.

Overlapping stent-assisted coil embolization for a ruptured intracranial vertebral artery dissection.

Ruptured intracranial vertebral artery dissection is a cause of non-traumatic subarachnoid hemorrhage. Urgent intervention should be considered to prevent fatal rebleeding. Endovascular parent artery occlusion, which is the initial treatment of choice, is not suitable for patients with a hypoplastic or occlusive contralateral vertebral artery. We report a case of ruptured vertebral artery dissection, which was successfully treated with double overlapping stent-assisted coiling.

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.

Patient-specific cortical electrodes for sulcal and gyral implantation.

PURPOSE: Noninvasive localization of certain brain functions may be mapped on a millimetre level. However, the interelectrode spacing of common clinical brain surface electrodes still remains around 10 mm. Here, we present details on development of electrodes for attaining higher quality electrocorticographic signals for use in functional brain mapping and brain-machine interface (BMI) technologies. METHODS: We used platinum-plate-electrodes of 1-mm diameter to produce sheet electrodes after the creation of individualized molds using a 3-D printer and a press system that sandwiched the electrodes between personalized silicone sheets. RESULTS: We created arrays to fit the surface curvature of the brain and inside the central sulcus, with interelectrode distances of 2.5 mm (a density of 16 times previous standard types). Rat experiments undertaken indicated no long term toxicity. We were also able to custom design, rapidly manufacture, safely implant, and confirm the efficacy of personalized electrodes, including the capability to attain meaningful high-gamma-band information in an amyotrophic lateral sclerosis patient. CONCLUSION: We developed cortical sheet electrodes with a high-spatial resolution, tailor-made to match an individual's brain. SIGNIFICANCE: This sheet electrode may contribute to the higher performance of BMI's.

Severely affected ALS patients have broad and high expectations for brain-machine interfaces.

Brain-machine interfaces (BMIs) may provide new communication channels and motor function to individuals with severe neurodegenerative diseases, but little is known about their interests in such devices. We investigated the interests of severely affected ALS patients in BMIs, and examined factors that might influence these interests. We conducted an anonymous, mail-back questionnaire survey of severely disabled ALS patients diagnosed using the revised El Escorial criteria. Thirty-seven patients responded to the questionnaire. Twenty-nine (78.4%) had undergone tracheostomy positive pressure ventilation. More than 80% of the patients were interested in communication support. Thirty-three (89.2%) felt stressed during communication. Among those using assistive communication devices (17 patients), 15 (88.2%) were not satisfied with them. More than 50% of the patients expressed an interest in BMIs. Their expectations of BMIs ranged widely from emergency alarm to postural change. The frequent use of personal computers tended to be correlated with an interest in invasive BMIs (p = 0.07). In conclusion, this was the first questionnaire survey demonstrating that severely affected ALS patients have broad and high expectations for BMIs. Communication was the most desired support from BMIs for such patients. We need to meet their widely ranging expectations of BMIs.

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 (Cronbach's 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.

Patient-specific contour-fitting sheet electrodes for electrocorticographic brain machine interfaces.

Non-invasive localization of certain brain functions may be mapped on a millimeter level. However, the inter-electrode spacing of common clinical brain surface electrodes still remains around 10 mm, and some electrodes fail to measure cortical activity due to unconformable plain electrode sheets. Here, we present details on development of implantable electrodes for attaining higher quality electrocorticographic signals for use in functional brain mapping and brain-machine interfaces. We produced personalized sheet electrodes after the creation of individualized molds using a 3D-printer. We created arrays to fit the surface curvature of the brain and inside the central sulcus, with inter-electrode distances of 2.5 mm. Rat experiments undertaken indicated no long term toxicity. We were also able to custom design, rapidly manufacture, safely implant and confirm the efficacy of personalized electrodes, including the capability to attain meaningful high gamma-band information in an amyotrophic lateral sclerosis patient. This sheet electrode may contribute to the higher performance of BMI's.

Which is the most appropriate disconnection surgery for refractory epilepsy in childhood?

Children with unilobar or multilobar pathology issuing in refractory epilepsy are potential candidates for surgical treatment. Extensive surgery results in good seizure control, but it also increases the risk of neurological deficits as well as motor and mental problems. We reviewed the cases of 19 children with refractory epilepsy treated surgically at Osaka University Hospital. Four of the 19 patients underwent temporal disconnection, 2 underwent occipital lobectomy, 4 underwent temporoparietooccipital disconnection, 6 underwent functional hemispherotomy, and 3 underwent corpus callosotomy. A good surgical outcome, i.e., Engel's class I or II, was achieved in 12 (63%) of the 19 patients. Excellent surgical outcomes and satisfactory motor and mental development were achieved in 4 patients who underwent temporoparietooccipital disconnection. The outcomes of functional hemispherectomy were also satisfactory. The outcomes of temporal disconnection and corpus callosotomy were poor in comparison to outcomes of the other procedures. We believe that better surgical outcomes would have been achieved with temporoparietooccipital disconnection in some cases treated by temporal disconnection or occipital resection. Adequate extensive surgical procedures should be considered for refractory childhood epilepsy arising from unilobar or multilobar pathology.

High-frequency repetitive transcranial magnetic stimulation over the primary foot motor area in Parkinson's disease.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been reported to be clinically effective for treating motor symptoms in Parkinson's disease (PD). Few studies have been performed reporting the effects of rTMS on non-motor symptoms such as depression and apathy in PD. OBJECTIVE: We assessed the effects of high-frequency (HF) rTMS over the primary motor (M1) foot area on motor symptoms, depression and apathy scales, and sensory symptoms in PD. METHODS: We investigated the efficacy of 3 consecutive days of HF-rTMS over the M1 foot area in 21 patients with PD using a randomized, double-blind cross-over trial compared with sham stimulation. Motor effects were evaluated using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the self-assessment motor score, the visual analog scale (VAS), the 10-m walking test, and finger tapping. Non-motor effects were analyzed using the Montgomery Asberg Depression Rating Scale, the Apathy Scale, and quantitative sensory testing. RESULTS: HF-rTMS significantly improved UPDRS-III (P < 0.001), VAS (P < 0.001), the walking test (P = 0.014), self-assessment motor score (P = 0.010), and finger tapping measurement (P < 0.05) compared to sham stimulation. In contrast, no significant improvement was observed in depression and apathy scales. Consecutive days of rTMS did not significantly increase the improvement in motor symptoms. There were no adverse effects following rTMS on patients with PD. CONCLUSIONS: We confirmed that HF-rTMS over the M1 foot area significantly improved motor symptoms in patients with PD. In addition, daily repeated stimulation was not significantly more effective than a single session of stimulation, but may be effective for maintaining the improvement in motor symptoms in patients with PD.

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

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.

Differential efficacy of electric motor cortex stimulation and lesioning of the dorsal root entry zone for continuous vs paroxysmal pain after brachial plexus avulsion.

BACKGROUND: Pain after traumatic brachial plexus avulsion (BPA) has 2 distinct patterns: continuous burning pain and paroxysmal shooting pain. Lesioning of the dorsal root entry zone (DREZotomy) is more effective for paroxysmal than continuous pain. It is unknown, however, whether electric motor cortex stimulation (EMCS) has a differential effect on continuous vs paroxysmal BPA pain. OBJECTIVE: To analyze the differential effect of EMCS and DREZotomy on continuous vs paroxysmal BPA pain in a series of 15 patients. METHODS: Fifteen patients with intractable BPA pain underwent DREZotomy alone (n = 7), EMCS alone (n = 4), or both procedures (n = 4). Pain intensity was evaluated with the Visual Analog Scale, and separate ratings were recorded for paroxysmal and continuous pain. Pain relief was categorized as excellent (> 75% pain relief), good (50%-75%), or poor (< 50%). Favorable outcome was defined as good or better pain relief. RESULTS: Eight patients had EMCS; 7 were followed up for an average of 47 months. Of those 7 patients, 3 (42%) with continuous pain had favorable outcomes compared with no patients with paroxysmal pain. Eleven patients had DREZotomy; 10 were followed up for an average of 31 months. Of those 10 patients, 7 (70%) with paroxysmal pain had favorable outcomes compared with 2 (20%) with continuous pain. CONCLUSION: EMCS was ineffective for paroxysmal pain but moderately effective for continuous pain. DREZotomy was highly effective for paroxysmal pain but moderately effective for continuous pain. It may be prudent to use EMCS for residual continuous pain after DREZotomy.

Spray-irrigation system attached to high-speed drills for simultaneous prevention of local heating and preservation of a clear operative field in spinal surgery.

Heat generation due to drilling during spinal surgery is potentially hazardous to nerves. Saline irrigation is often performed to prevent such local heating, but sometimes floods and obscures the operative field. We have developed a spray-irrigation system for attachment to high-speed drills, which sprays saline solution with an air-jet in the direction of the surface cut by the drill. We anticipated that this air jet would create a clearer operative view by displacing excess fluid, and would also provide an added cooling effect greater than that of irrigation with saline. This study was designed to evaluate these predicted effects of the spray-irrigation system compared to conventional irrigation. A thermography study was performed to confirm the cooling effect of the spray-irrigation system. A plaster board coated with adhesives was drilled at 100,000 rpm along a 10-cm line for a duration of 20 seconds. Thermograms were recorded every minute, without cooling, with irrigation, and with the spray-irrigation system. To examine the operative views, continuous drilling for a period of seconds was performed with conventional irrigation and with the spray-irrigation system. Local heating was inhibited by the spray-irrigation system to 14-30% of that with irrigation. A clear operative field was maintained during continuous drilling using the spray-irrigation system through the air-jet action of the system. The spray-irrigation system can simultaneously provide effective cooling and a clear operative field during surgical manipulations with high-speed drills.

Allodynia corresponding to the levels of cervical cord injury treated by surgical decompression: a report of 3 cases.

BACKGROUND: The role and timing of surgical decompression for SCI remains controversial, when the surgical outcomes are evaluated only by neurologic recovery. Other than neurologic deficits, severe pain after SCI is a significant problem, deteriorating the patient's activity of daily living. In the present report, allodynia of patients' upper limbs caused by cervical SCI was treated successfully by surgical decompression. CASE DESCRIPTIONS: Three male patients received cervical SCI through minor accidents. They complained of allodynia and motor dysfunction at the spinal level compressed by preexisting lower cervical spondylosis, but they lacked symptoms or neurologic abnormalities below that spinal level. Severe pain was induced by soft touch or exposure to water at room temperature preoperatively. Surgical decompressions of the spinal cord and nerve roots were performed between 20 and 83 days (mean, 48.7 days) after the SCI. Allodynia was reduced in all patients immediately after surgery. Pain induced by soft touch disappeared within 4 days of operations, whereas pain by water exposure diminished within months. Recurrence of allodynia has not been observed in patients at least until the last follow-up, within periods ranging from 15 to 39 months (average, 26 months). The mean preoperative VAS was 6.0, and this improved to 2.2 at 1 month and 0.8 at the final follow-up. CONCLUSION: We propose that patients with SCI with allodynia and motor dysfunction of the upper limbs related only to the compressed spinal levels are potentially treatable by surgical decompression.

Microscopic bilateral decompression through unilateral laminotomy for lumbar canal stenosis in patients undergoing hemodialysis.

OBJECT: Microscopic bilateral decompression through a unilateral laminotomy (MBDUL) is a minimally invasive technique used to treat lumbar canal stenosis (LCS). In the present study, MBDUL was performed to treat LCS in eight patients undergoing hemodialysis. METHODS: Surgical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scale (highest possible score 29). The JOA scale was administered preoperatively, at 1 month and 3 months postoperatively, and at the final follow-up examination. One patient refused to undergo the postoperative assessment after the 1-month examination; the mean follow-up duration of the remaining seven patients was 24 months (range 18-31 months). The mean age at the time of surgery was 62 years (range 48-76 years), and the mean duration of hemodialysis therapy was 21.4 years (range 3-28 years). All patients could walk within 2 days of surgery. The mean angle of the straight leg-raising (SLR) test was 53.8 degrees preoperatively, and this increased to 69.4 degrees postoperatively. Six patients felt enhancement of sciatica or leg pain when performing the SLR test preoperatively, a finding that was absent postoperatively at least until the final follow-up examination. The mean preoperative JOA score was 11.6 (range 4-22), and the score markedly improved to 19.8 (range 15-23) at 1 month and 20.6 (range 16-25) at 3 months. The mean JOA score decreased to 17.1 (range 12-25) at the final follow-up examination, but this decrease was attributed to other physical disorders. CONCLUSIONS: The authors conclude that MBDUL is a safe and effective surgical treatment for patients undergoing hemodialysis who are suffering from LCS.

Giant intrasellar arachnoid cyst manifesting as adrenal insufficiency due to hypothalamic dysfunction--case report--.

A 67-year-old man first noticed loss of pubic and axillary hair in 1992 and then a visual field defect in 2001. He experienced loss of consciousness attributed to hyponatremia in April 2002. Magnetic resonance imaging showed a giant intrasellar cystic mass, 40 mm in diameter, that had compressed the optic chiasm. The patient complained of chronic headache, and neurological examination revealed bitemporal hemianopsia. Preoperative endocrinological examination indicated adrenal insufficiency, and hypothyroidism due to hypothalamic dysfunction. The patient underwent endonasal transsphenoidal surgery. The cyst membrane was opened and serous fluid was drained. Histological examination identified the excised cyst membrane as arachnoid membrane. The patient's headaches resolved postoperatively, but the bitemporal hemianopsia and endocrinological function were unchanged. This arachnoid cyst associated with hypothalamic dysfunction might have been caused by an inflammatory episode in the suprasellar region.