Search

There have been limited studies regarding stereotactic and functional neurosurgery for lingual dystonia. Here, we report a patient with primary lingual dystonia who showed significant improvement after bilateral deep brain stimulation (DBS). A 42-year-old woman presented with a 5- to 6-year history of tongue protrusion; however, she lacked a significant medical or medication history before onset. She presented with gradually worsening symptoms and was diagnosed with idiopathic lingual dystonia. Her tongue was injected with botulinum toxin on 6 occasions; however, it had a limited effect. Oral medications were ineffective. She underwent DBS since her involuntary tongue movements were causing nocturnal breathing problems. Directional leads were bilaterally inserted into the internal segment of the globus pallidus (GPi). The directional part of each lead was inserted at the GPi bottom on both sides. The posteromedial contacts were used to deliver stimulation. After 1.5 years, the patient’s Burke-Fahn-Marsden dystonia rating scale score improved from 9 to 1.5 and 2 to 1 for movement and disability, respectively. This case demonstrated the effectiveness of bilateral GPi-DBS. Placing the directional part of the lead in the GPi bottom could improve the stimulation effects.

The hanger reflex is a phenomenon characterized by the involuntary rotation of the head when a wire hanger is worn around the head such that a force is applied to the frontal temporal area by the longer side of the hanger. The application of a shearing force on the skin is thought to be the cause of this phenomenon. Attempts have been made to treat cervical dystonia using equipment designed to induce the hanger reflex. This reflex may have implications in the treatment of headaches, cervical pain, and adhesive capsulitis. The hanger reflex is seen not only in the head region but is also in other parts of the body. Thus, it could be used in the treatment of systemic dystonias. The hanger reflex may help develop inexpensive and non-invasive treatment for dystonia or other neurological diseases and is expected to be the focus of research in the future.

Background Approximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated the safety, pharmacokinetics, pharmacodynamics, and efficacy of DS-1001. Methods This was a multicenter, open-label, dose-escalation, phase I study of DS-1001 for recurrent/progressive IDH1-mutant (R132) glioma (N = 47) (NCT03030066). DS-1001 was administered orally at 125-1400 mg twice daily. Dose-escalation used a modified continual reassessment method. Results The maximum tolerated dose was not reached. Eight patients were continuing treatment at the data cutoff. Most adverse events (AEs) were grade 1-2. Twenty patients (42.6%) experienced at least 1 grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, and dry skin. The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Median progression-free survival was 10.4 months (95% confidence interval [CI], 6.1 to 17.7 months) and not reached (95% CI, 24.1 to not reached) for the enhancing and non-enhancing glioma cohorts, respectively. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples. Conclusions DS-1001 was well tolerated with a favorable brain distribution. Recurrent/progressive IDH1-mutant glioma patients responded to treatment. A study of DS-1001 in patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 glioma is ongoing (NCT04458272).

Stereotactic and functional neurosurgery(deep brain stimulation[DBS]and radiofrequency coagulation)is an established method of treatment for patients with Parkinson's disease, tremor, and/or dystonia. The surgery involves many pitfalls and is similar to other surgeries, requiring experience and skills. Here, we have discussed three categories of DBS-related complications, including surgical procedure-related and device-related complications, and stimulation-induced side effects. In addition, we have discussed the prevention and coping methods, including those not listed in the guidelines for stereotactic and functional neurosurgery.

OBJECTIVE Directional leads are used for deep brain stimulation (DBS). Two of the four contacts of the leads are divided into three parts, enabling controlled stimulation in a circumferential direction. The direction of adverse effects evoked by DBS in the subthalamic nucleus (STN) and stimulation strategies using directional leads were evaluated. METHODS Directional leads were implanted into the bilateral STN of six parkinsonian patients (1 man, 5 women; mean age 66.2 years). The contact centers were located within the upper border of the STN, and the locations were identified electrically using microrecordings. Adverse effects were evaluated with electrical stimulation (30 μs, 130 Hz, limit 11 mA) using the directional part of each lead after surgery, and the final stimulation direction was investigated. Unified Parkinson's disease rating scale (UPDRS) scores were evaluated before and after DBS. RESULTS Fifty-six motor and four sensory symptoms were evoked by stimulation; no adverse effect was evoked in 14 contacts. Motor and sensory symptoms were evoked by stimulation in the anterolateral direction and medial to posterolateral direction, respectively. Stimulation in the posteromedial direction produced adverse effects less frequently. The most frequently used contacts were located above the STN (63%), followed by the upper part of the STN (32%). The mean UPDRS part III and dyskinesia scores decreased after DBS from 30.2 ± 11.7 to 7.2 ± 2.9 and 3.3 ± 2.4 to 0.5 ± 0.8, respectively. CONCLUSION The incidence of adverse effects was low for the posteromedial stimulation of the STN. Placing the directional part of the lead above the STN may facilitate the control of dyskinesia.

We showed the results of pathological and genetic investigation for an autopsy case who was evaluated as longstanding Parkinson's disease (PD) in alive. Neuropathological investigation showed "pure nigropathy" without Lewy and tau pathology, and genetic analyses using next-generation sequencing detected novel TUBA4A nonsence mutation. Subsequent physiological study added to strength the hypothesis that the variant is pathogenic one. Present case showed TUBA4A is not only responsible gene for amyotrophic lateral sclerosis/frontotemporal dementia but also PD associated pure nigropathy. Also we found minimal but significant tau pathology high possibly associated with long-term deep brain stimulation in subthalamic nucleus.

We report two cases of granuloma that occurred around an implantable pulse generator (IPG) for deep brain stimulation. Both cases showed no signs of infection and disappeared after moving the IPG and removing the granulation. If a noninfectious mass is formed, the relocation of IPG may improve it.

Ventro-oral (Vo) thalamotomy is effective in patients with focal task-specific dystonias (FTSDs), but only in those with upper-limb symptoms. We describe a patient with drummer's dystonia who completely recovered after Vo thalamotomy. A 37-year-old man who started playing drums at 14 began having difficulty performing fine movements with his right foot when drumming at 22. He experienced right hand cramps while drumming 3 months before visiting our hospital. He was diagnosed with FTSD. Left Vo thalamotomy was performed, which led to complete improvement of symptoms. Vo thalamotomy may be effective for FTSD patients with upper- and lower-extremity symptoms.

The hanger reflex (HR) is an involuntary head rotation that occurs in response to a clothes hanger encircling the head and compressing the unilateral fronto-temporal area. Here, we developed an elliptical device to induce the HR and examined its utility for the treatment of cervical dystonia (CD). The study included 19 patients with rotational-type CD. The device was applied to each subject’s head for at least 30 min/day for 3 months. Severity scores on part 1 of the Toronto Western Spasmodic Torticollis Rating Scale were evaluated at baseline and after the 3-month trial. Mean scores without and with the device were significantly different both at baseline (16.6 vs. 14.7, respectively; P < 0.05) and after the trial (14.9 vs. 13.6, respectively; P < 0.05). This preliminary trial suggests that our device can improve abnormal head rotation in patients with CD.

Background Stereotactic ventro-oral thalamotomy has been performed in cases of focal task-specific dystonia, including writer's cramp, with excellent outcomes. However, no reports have revealed the outcome of ventro-oral thalamotomy in a patient with a contralateral cerebral lesion. We describe a patient with left-hand writer's cramp with an old lesion in the left hemisphere and transient gait disturbance after right ventro-oral thalamotomy. Case Description A 43-year-old man had a hemorrhage in the left basal ganglia due to cerebral arteriovenous malformation at 22 years of age, and right hemiparesis remained as a sequela. He developed left-handed writing ability; however, he became aware of the stiffness of his left hand and difficulty in writing. Writer's cramp was diagnosed. Medical treatments were not effective, and right ventro-oral thalamotomy was performed. Although his writing ability improved, he could not walk. After performing rehabilitation, his walking completely improved, reaching the level before surgery, after 3 months, and his writer's cramp was completely cured. Conclusions In patients with basal nucleus lesions, gait disturbance may appear transiently after contralateral thalamotomy. It is crucial to fully explain the potential complications, particularly in relation to temporal gait disturbances, and obtain informed consent.

Why a catheter can be correctly placed in the ventricle by inserting perpendicular to the frontal bone on the ventricular drainage? We performed a study on the accuracy of a path perpendicular to the skull surface into the anterior horn using computed tomography (CT), and a clinical study. Twenty patients were studied on CT images. Using the curved multi-planar reconstruction method, the curved frontal skull and brain were reconstructed to flat structures, and perpendicular lines were drawn from the flat surface to the foramen of Monro on the reconstructed images. In clinical practice, we made a device which guided a catheter inserting perpendicular to the frontal skull surface, and used it in the ventricular drainage surgery for 148 hydrocephalic patients (158 surgeries). We discovered that the curved surface of the frontal bone around Kocher’s point represents the surface of a globe (mean radius, 75.9 ± 4.3 mm) centering on the foramen of Monro. The distribution of points ranged from 13.5–43.5 mm (mean, 43.5 ± 6.1 mm) to the midline, with points appearing more laterally as ventricular size increased. A catheter was placed in the ventricle in 148 surgeries (99.4%), and the catheter reached the ventricle with correct orientation toward the foramen of Monro in 128 (81.0%). The reason why the ventricular insertion perpendicular to the frontal bone surface can provide a consistent path toward the foramen of Monro is that the curved surface of the frontal bone around Kocher’s point represents the surface of a globe centered on the foramen of Monro.

We report the discovery of a potent and isozyme-selective MTHFD2 inhibitor, DS18561882 (2). Through investigation of the substituents on our tricyclic coumarin scaffold (1,2,3,4-tetrahydrochromeno[...

Background Granulocyte colony-stimulating factor (G-CSF) has shown neuroprotective and neurogenerative activities in experimental studies, and our previous phase I clinical study suggested the safety and potential efficacy of low-dose G-CSF in acute ischemic stroke patients. The present phase II trial is aimed to evaluate the effect of G-CSF administration on neurological function and infarct volume, compared with a placebo group. Methods Forty-nine acute ischemic stroke patients (29 males, 20 females; 71 ± 10 years) within 24 hours after onset were recruited. Eligible patients were randomized 2:2:1 to receive G-CSF 150 µg/body/day, G-CSF 300 µg/body/day, and placebo, respectively. We evaluated clinical outcome in terms of the National Institutes of Health Stroke Scale, the modified Rankin Scale, and the Barthel Index at 90 days after onset, together with changes in infarct volume on magnetic resonance imaging. Results We found no serious adverse event, including change in leukocyte levels, which remained below 31,000/µL, at 150 and 300 µg G-CSF/body/day. Clinical outcome scores did not show any significant difference among the 3 groups. Chronological changes in infarct volume also showed no significant difference. Conclusions G-CSF was well-tolerated at 150 and 300 µg/body/day in patients with acute ischemic stroke. However, administration of G-CSF at both 150 and 300 µg/body/day neither contributed to functional recovery nor reduced infarct volume at 3 months after onset, compared with the control group. The apparent lack of effectiveness may have been due to the small sample size. A trial of combination therapy with recombinant tissue plasminogen activator and G-CSF is planned.

(123)I-ioflupane SPECT (DaTscan) is an examination that detects presynaptic dopamine neuronal dysfunction, and has been used as a diagnostic tool to identify degenerative parkinsonism. Additionally, myocardial (123)I-metaiodobenzyl guanidine (MIBG) scintigraphy measures the concentration of cardiac sympathetic nerve fibers and is used to diagnose Parkinson's disease (PD). These exams are used as adjuncts in the diagnosis of parkinsonism, however, the relationship of these two examinations are not well-known. We investigated the relationship of these two scanning results specifically for determining the use of deep brain stimulation therapy (DBS). Subjects were Japanese patients with suspected striatonigral degeneration, including PD; DaTscans and myocardial MIBG scintigraphy were performed. The mean values of the left-right specific binding ratios (SBRs) from the DaTscan, and the early/delayed heart-to-mediastinum ratios (HMRs) from the MIBG scintigraphy were calculated. Using simple linear regression analysis, we compared the SBR and early/delayed HMR values. Twenty-four patients were enrolled in this study. Twenty-one patients were positive via the DaTscan, and the MIBG scintigraphy results showed 14 patients were positive. SBR and both early and delayed HMR were positively correlated in cases of PD, but negative in non-PD cases. A mean SBR value less than 3.0 and a delayed HMR value less than 1.7 indicated a Hoehn-Yahr stage 3 or 4 for PD, which is commonly regarded as a level appropriate for initiating DBS therapy. Our results indicate that performing both DaTscan and MIBG scintigraphy is useful for the evaluation of surgical intervention in PD.

Five recent multicenter randomized controlled trials (RCTs) have clearly shown the superiority of mechanical thrombectomy in large vessel occlusion acute ischemic stroke compared to systemic thrombolysis. Although 14 hospitals in Ishikawa prefecture have uninterrupted availability of systemic thrombolysis, mechanical thrombectomy is not available at all of these hospitals. Therefore, we established a Kanazawa mobile embolectomy team (KMET), which could travel to these hospitals and perform the acute reperfusion therapy. In this article, we report early treatment outcomes and validate the effectiveness of a network between affiliated hospitals and KMET. Between January 2014 and December 2015, 48 patients, aged 45–92 years (mean: 73.0 years), underwent acute reperfusion therapy provided by KMET in 10 affiliated hospitals of Kanazawa University Hospital. The pre-treatment NIHSS scores ranged from 5 to 39 (mean: 19.1). ASPECTS+W ranged from 1 to 11 (mean: 7.3). Successful revascularization, defined as thrombolysis in cerebral infarction (TICI) 2b or 3, was achieved in 38/48 cases (80%), and a good outcome, defined as modified Rankin Scale (mRS) score from 0 to 2 at 90 days after the treatment, was achieved in 24/48 cases (50%). There were two cases of intracranial bleeding (4%). Mean time from onset to recanalization was 297 min. These results, which are similar to those of five previous RCTs, suggest that a collaborative network between affiliated hospitals and KMET is effective for acute reperfusion therapy in local areas wherein experienced neuroendovascular specialists are insufficient.

When the head is encircled with a wire clothes hanger and the unilateral fronto-temporal region is compressed, the head rotates unexpectedly. As the mechanism is unclear, however, we have temporarily named this phenomenon as the "hanger reflex." We previously reported a case wherein this phenomenon was applied to treat cervical dystonia. Because little is known about this phenomenon, we determined how often this phenomenon is observed in healthy subjects. Study participants were 120 healthy Japanese adults (60 men and 60 women) aged 19-65 years. A wire clothes hanger was applied to each subject's head. The longer side of the hanger was attached over the volunteer's fronto-temporal regions on both sides of the head in succession (i.e., two applications per volunteer). We evaluated whether the subjects felt the sensation of head rotation by using a questionnaire. The sensation of head rotation was observed in 95.8% of subjects. There were five non-responders (4.2%). In 85.4% of the trials, head rotation was observed in the direction that coincided with the side compressed by the hanger. There were no differences in responses between genders. The incident rate of the hanger reflex was remarkably high and most likely represents a prevalent phenomenon in humans. The mechanism underlying the reflex remains unknown. Further research should be performed to elucidate the underlying causes of the hanger reflex, which represents a potential treatment for cervical dystonia.

The hanger reflex is a phenomenon in which the head involuntarily rotates when force is applied via a wire hanger placed on the head. The application of pressure to particular points of the head is necessary to induce this phenomenon, which occurs when shear deformation of the skin induces illusory force perception. Because the hanger reflex represents the induction of force and motion using a simple device, and has been found in other body parts such as the wrist, waist, and ankle, it is expected to be useful as an application in haptic interface technology. In this paper, we describe new directions of force associated with the hanger reflex; four translation, and two rotational directions of the head, and four translation and one rotational direction of the waist.

Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic intermediates as building blocks for biosynthetic processes, and thereby supporting cell proliferation. Activation of PKM2 should invert aerobic glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has gained attention as a promising cancer therapy target. To obtain novel PKM2 activators, we conducted a high-throughput screening (HTS). Among several hit compounds, a fragment-like hit compound with low potency but high ligand efficiency was identified. Two molecules of the hit compound bound at one activator binding site, and the molecules were linked based on the crystal structure. Since this linkage succeeded in maintaining the original position of the hit compound, the obtained compound exhibited highly improved potency in an in vitro assay. The linked compound also showed PKM2 activating activity in a cell based assay, and cellular growth inhibition of the A549 cancer cell line. Discovery of this novel scaffold and binding mode of the linked compound provides a valuable platform for the structure-guided design of PKM2 activators.

Previously, we reported on the differentiation between patients with Alzheimer disease and normal controls using a quantitative electroencephalographic technique called neuronal activity topography (NAT). In this technique, cerebral neuronal activities are characterized by the signal intensity and coherence (sNAT and vNAT, respectively). In the present study, we examined 47 patients with vascular cognitive impairment in carotid stenosis and 52 normal controls. All subjects underwent electroencephalography in a resting state with closed eyes for 5 minutes. Electroencephalographic markers of the differential likelihood, that is, the sensitivity-versus-specificity characteristics, sL(x:VCI-NLc) and vL(x:VCI-NLc), were assessed with neuronal activity topography and were compared between the 2 groups. sL(x:VCI-NLc) and vL(x:VCI-NLc) crossed each other at a cutoff value of the differential likelihood. Separation of the patients and controls was made with a sensitivity of 92% and 88%, as well as a false-positive rate of 8% and 12% for sL(x:VCI-NLc) and vL(x:VCI-NLc), respectively. Using sNAT, we accurately differentiated 92% patients with vascular cognitive impairment. We recommend that sNAT, rather than vNAT, should be used in detecting vascular cognitive impaired patients.

Background Task-specific focal dystonia, such as writer's cramp and musician's cramp, is a type of dystonia that affects performance of particular tasks. Such movement disorders have been treated with stereotactic ventro-oral (Vo) thalamotomy with excellent outcomes. However, there has been no previous report of treatment of sport-related or athlete's dystonia by means of stereotactic surgery. We treated a patient with table tennis–related dystonia with Vo thalamotomy, and evaluated the outcome. Case Description A 20-year-old, female, left-handed table tennis player complained of difficulty hitting a ping-pong ball. She started playing table tennis at 8 years of age, practiced for more than 4 hours every day, and participated in national tournaments. Abnormal flexion of the left wrist when hitting a ball became apparent when she was 19 years old. The abnormal movement emerged on the forehand stroke and, subsequently, on the backhand, until finally she could not continue playing. The diagnosis was task-specific focal dystonia that did not recover with medication. She visited our hospital and underwent right Vo thalamotomy. The surgery was performed using local anesthesia, with the patient swinging a paddle during stimulation and coagulation of the thalamus. Her symptoms had improved completely the day after surgery, such that she was able to participate in tournaments again. Conclusions We applied Vo thalamotomy for the successful treatment of athlete's dystonia, suggesting that this condition has an underlying mechanism similar to that of other task-specific focal dystonias. This provides new hope to patients with athlete's dystonia refractive to other therapies.

(123)I-ioflupane SPECT (DaTscan) is an examination that detects presynaptic dopamine neuronal dysfunction, and has been used as a diagnostic tool to identify degenerative parkinsonism. Additionally, myocardial (123)I-metaiodobenzyl guanidine (MIBG) scintigraphy measures the concentration of cardiac sympathetic nerve fibers and is used to diagnose Parkinson's disease (PD). These exams are used as adjuncts in the diagnosis of parkinsonism, however, the relationship of these two examinations are not well-known. We investigated the relationship of these two scanning results specifically for determining the use of deep brain stimulation therapy (DBS). Subjects were Japanese patients with suspected striatonigral degeneration, including PD; DaTscans and myocardial MIBG scintigraphy were performed. The mean values of the left-right specific binding ratios (SBRs) from the DaTscan, and the early/delayed heart-to-mediastinum ratios (HMRs) from the MIBG scintigraphy were calculated. Using simple linear regression analysis, we compared the SBR and early/delayed HMR values. Twenty-four patients were enrolled in this study. Twenty-one patients were positive via the DaTscan, and the MIBG scintigraphy results showed 14 patients were positive. SBR and both early and delayed HMR were positively correlated in cases of PD, but negative in non-PD cases. A mean SBR value less than 3.0 and a delayed HMR value less than 1.7 indicated a Hoehn-Yahr stage 3 or 4 for PD, which is commonly regarded as a level appropriate for initiating DBS therapy. Our results indicate that performing both DaTscan and MIBG scintigraphy is useful for the evaluation of surgical intervention in PD.

Background: Few multiple case studies of the effects of deep brain stimulation for camptocormia associated with Parkinson’s disease have been reported. Although deep brain stimulation was in some cases not effective against camptocormia, it is unclear in which types of patients it was effective in treating camptocormia. Objective: We treated 4 Parkinson’s disease patients with camptocormia and evaluated their paraspinal muscle status by computed tomography to specify the characteristics of cases of effective treatment. Methods: The 2 female and 2 male patients in this study were 60–69 years old, with a disease duration from onset to surgery of 7–13 years and a follow-up period of 18–40 months. The electrodes were implanted bilaterally in the subthalamic nuclei. Results: Camptocormia was improved in 3 cases, and was unchanged in the remaining case although other parkinsonian symptoms improved. The computed tomography number of paraspinal muscle in the unimproved patient was much smaller than that in the improved patients. Conclusions: A relationship may exist between improvement of camptocormia and severity of paraspinal muscle degeneration.

症例1 : 63歳, 男性. 右完全片麻痺, 全失語にて発症. CTにて明らかな異常を認めず, 脳血管撮影にて巨大塞栓子による左頚部内頚動脈閉塞を認めた. 血栓の脇にカテーテルを進め末梢側で造影したところ, 内頚動脈分岐部で閉塞を認めた. 末梢部の血栓溶解を施行し側副血行路を開通させ, 症状の回復が見られたが, 2日後に頚部血栓が末梢へ移動し, 高度の後遺症が残存した. 症例2 : 79歳, 男性. 右不全片麻痺, 失語にて発症. 脳血管撮影では, 巨大塞栓子による左頚部内頚動脈閉塞を認め, 側副血行により左中大脳動脈が描出された. 左内頚動脈が逆行性に錐体部まで描出されていたため, 緊急で頚動脈血栓摘出術を施行し, 術後, 症状の改善が見られた. 巨大塞栓子による急性期頚部内頚動脈閉塞症は稀な疾患であり, 血栓溶解療法による再開通が困難で, 開通した場合でも末梢塞栓を起こしやすい. われわれが経験した2症例を踏まえ, 治療フローチャートを提唱する.

Myeloperoxidase (MPO)-generated halogenating molecules, such as hypochlorous acid and hypobromous acid (HOBr), in inflammatory regions are postulated to contribute to disease progression. In this study, we showed that ergothioneine (EGT), derived from an edible mushroom, inhibited MPO activity as well as the formation of 8-bromo-2′-deoxyguanosine in vitro. The HOBr scavenging effect of EGT is higher than those of ascorbic acid and glutathione. We initially observed that the administration of Coprinus comatus, an edible mushroom containing a high amount of EGT, inhibited the UV-B-induced inflammatory responses and DNA halogenation, suggesting that EGT is a promising anti-inflammatory agent from mushrooms.

At the sites of inflammation, hypohalous acids, such as hypochlorous acid and hypobromous acid (HOBr), are produced by myeloperoxidase. These hypohalous acids rapidly react with the primary amino groups to produce haloamines, which are relatively stable and can diffuse long distances and cross the plasma membrane. In this study, we examined the effects of taurine, the most abundant free amino acid in the leukocyte cytosol, on the hypohalous acid-dependent formation of 8-chloro-2'-deoxyguanosine (8-CldG) and 8-bromo-2'-deoxyguanosine (8-BrdG). The reaction of taurine with HOBr yielded taurine bromamine, which is the most stable among other bromamines of amino acids. Taurine also enhanced the bromination of only dG among the four 2'-deoxynucleosides, whereas it inhibited the 8-CldG formation. The specificity of taurine for the enhanced formation of halogenated dG is completely different from that of nicotine, an enhancer of chlorination. The amount of dibrominated taurine (taurine dibromamine) closely correlated with the formation of 8-BrdG, suggesting that taurine dibromamine might be a plausible mediator for the dG bromination in vivo.

Typically, intrathecal baclofen therapy(ITB)for spasticity is continuously required because the spasticity can recur if the ITB is stopped. Thus, an infusion pump for the ITB is permanently implanted. Some sporadic cases exhibiting remarkable improvements in their spasticity and consciousness disturbances have been reported after implanting the ITB pump. We experienced a rare case involving removal of the ITB pump after the spasticity resolved and the consciousness disturbances markedly improved. A 15-year-old girl developed a subarachnoid hemorrhage due to rupture of an aneurysm in the right anterior cerebral artery. Her initial Glasgow Coma Scale score was 4(E1V1M2). Trapping of the aneurysm and decompression craniotomy were performed. Subsequently, she underwent a tracheotomy, and a percutaneous gastrostomy(PEG)tube was implanted because of persistent consciousness disturbances. Cranioplasty and lumbar-peritoneal shunt for normal pressure hydrocephalus were performed after 1 month. An ITB pump was implanted to improve the spasticity observed mainly in the lower extremities 61 days after hemorrhage onset. Right hemiparesis remained due to Kernohan's notch. After transfer to the rehabilitation hospital, her consciousness disturbances and spasticity remarkably improved(1.9 to 1.0 and 3.5 to 1.0 on the Ashworth scale for the upper and lower extremities, respectively). The tracheostomy and PEG tubes were removed, and the baclofen dose was gradually reduced. She was completely off baclofen after 7 months, and she was discharged with a short leg brace and a cane for walking. The baclofen pump was then removed. In this case, temporary ITB improved the spasticity and consciousness disturbances.

For single-unit recording from the brain in monkeys, the precise determination of recording targets is essential. Although magnetic resonance imaging (MRI) has been used recently in several laboratories, it has been difficult to obtain three-dimensional information on a target from two-dimensional pictures, and, therefore, it has also been difficult to determine precise coordinates. We developed a new method for precisely determining target-area coordinates based on reconstructed rendering pictures made from three-dimensional MRI data. We also combined this method with magnetic resonance angiography to avoid severe vessel complications in recording experiments.

Liposorber is a column used for plasma purification that adsorbs low-density lipoproteins with high selectivity, while Selesorb is a column that selectively adsorbs anti-DNA antibodies, anticardiolipin antibodies, and immune complexes. Both columns are packed with carriers, where a dextran sulfate ligand is bound to porous cellulose beads. Liposorber is used to treat familial hypercholesterolemia (FH), peripheral arterial disease (PAD), and focal segmental glomerulosclerosis (FGS): Selesorb is used to treat systemic lupus erythematosus (SLE). Treatment utilizing both columns is being used effectively in patients with refractory disease that is resistant to pharmacotherapy.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma in adults. MFH occurrence in the bones of the skull is extremely rare, and, to our knowledge, it has not been reported in a patient with a history of craniotomy. A 69 year old woman presented with a large mass in the left fronto-temporal bone. The patient's medical history included a left fronto-temporal craniotomy 8 years prior to the present admission for neck clipping of an aneurysm of the left middle cerebral artery. Following preoperative work up, the skull tumor was resected, and pathology showed that the mass was composed of spindle-shaped fibroblastic cells arranged in a storiform pattern, and of numerous multinucleated giant cells. A diagnosis of MFH was established. The patient died of intracranial hemorrhage from a subsequent tumor 22 months after resection of the first tumor.

It is still unclear whether deep brain stimulation targeted to the bilateral subthalamic nucleus (STN-DBS) affects cognitive function in Parkinson's disease (PD). This prospective study was aimed to systemically evaluate the impact of bilateral STN-DBS on motor and cognitive functions in patients with PD. This study included totally 11 Japanese patients with medically intolerant PD. Neurological and cognitive status was precisely evaluated before and 1 year after bilateral STN-DBS, using unified Parkinson's disease rating scale (UPDRS), levodopa equivalent doses, mini-mental state examination (MMSE), Japanese adult reading test (JART), repeatable battery for the assessment of neuropsychological status (RBANS), and Wechsler adult intelligence scale-revised (WAIS-R). Preoperative RBANS and WAIS-R identified cognitive dysfunction that could not be detected by MMSE and JART. Before surgery, PD patients had significantly impaired immediate memory and attention. Motor function significantly improved 1 year after bilateral STN-DBS. Bilateral STN-DBS did not affect any score on cognitive examinations. However, postoperative improvements of total score on RBANS and performance intelligence quotient (PIQ) scores on WAIS-R were closely related to those of UPDRS part III off (R(2) = 0.61, P < 0.01; R(2) = 0.39, P < 0.05, respectively). These findings strongly suggest that bilateral STN-DBS may significantly improve cognitive function in a certain subgroup of patients whose therapeutic effects on motor function are prominent.

Background: Writer's cramp is a specific movement disorder with hand muscle cramps in writing, being classified into focal and action-specific dystonia. Stereotactic surgery, such as thalamotomy and deep brain stimulation (DBS), has been reported for writer's cramp; however, the number of reported cases is still scarce and surgical procedures are also controversial. Objectives: In this study, therefore, we present 2 patients who underwent thalamotomy for writer's cramp and systematically review the literature on stereotactic surgery for writer's cramp. Methods: Case reports and literature review are presented. Results: Both patients underwent ventral oral nucleus (Vo) thalamotomy safely. Their symptoms completely disappeared after surgery and did not recur during follow-up periods. In the literature, a total of 31 cases were surgically treated for writer's cramp. Stereotactic surgery included thalamotomy in 25 cases and DBS in 6. The target included the Vo in 17 cases, the ventral intermediate nucleus (Vim) in 3, and both Vo and Vim in 7. Both procedures markedly improved or resolved the symptoms. Transient neurological deficits were observed in 16.0% of patients after thalamotomy. Conclusions: The Vo may be the most effective target to treat writer's cramp. Both thalamotomy and DBS are feasible and effective, but thalamotomy would be a better option, especially in younger or high-risk patients.

A 55-year-old man presented with gait disturbance, incontinence, and back pain. He had a medical history of schizophrenia for the past 35 years. Computed tomography (CT) and magnetic resonance imaging suggested thoracic vertebral hemangioma. Dynamic CT incidentally detected a hepatic hemangioma. Laminectomy of T3 and T4, resection of the epidural hemangioma, and rigid instrumentation between T1 and T6 using rod and hook systems were performed. Postoperatively, his symptoms completely disappeared and the histological diagnosis was capillary hemangioma. Schizophrenic patients have diminished sensitivity to pain or other symptoms, so neurological symptoms may become severe. However, early and appropriate treatment can result in satisfactory neurological outcome. The patient had a rare association of vertebral hemangioma and hepatic hemangioma, which may be a chance occurrence.

Reactions of tris(methylsenleno)borane-SnCl4 with alkenes 1a–g gave α,β-bis(methylseleno)alkanes 2a–g, stereospecifically, and reactions with 1,3-dienes 1i–k afforded α,β-bis(methylseleno)alk-2-enes 2i–k, regioselectively.

Myeloperoxidase (MPO) generates reactive halogenating species that can modify DNA. The aim of this study was to investigate the formation of 8-halogenated 2'-deoxyguanosines (8- halo-dGs) during inflammatory events. 8-Bromo-2'-dG (8-BrdG) and 8-chloro-2'-dG (8-CldG) were generated by treatment of MPO with hydrogen peroxide at physiological concentrations of Cl(-) and Br(-). The formation of 8-halo-dGs with other oxidative stress biomarkers in lipopolysaccharide-treated rats was assessed by liquid chromatography tandem mass spectrometry and immunohistochemistry using a novel monoclonal antibody (mAb8B3) to 8-BrdG-conjugated keyhole limpet hemocyanin. The antibody recognized both 8-BrdG and 8-CldG. In the liver of lipopolysaccharide-treated rats, immunostaining for 8-halo-dGs, halogenated tyrosines, and MPO were increased at 8 h, whereas those of 8-oxo-2'-dG (8-OxodG) and 3-nitrotyrosine were increased at 24 h. Urinary excretion of both 8-CldG and 8-BrdG was also observed earlier than those of 8-OxodG and modified tyrosines (3-nitrotyrosine, 3-chlorotyrosine, and 3- bromotyrosine). Moreover, the levels of the 8-halo-dGs in urine from human diabetic patients were 8-fold higher than in healthy subjects (n = 10, healthy and diabetic, p < 0.0001), whereas there was a moderate difference in 8-OxodG between the two groups (p < 0.001). Interestingly, positive mAb8B3 antibody staining was observed in liver tissue from hepatocellular carcinoma patients but not in liver tissue from human cirrhosis patients. These data suggest that 8-halo-dGs may be potential biomarkers of early inflammation.

We have examined the antitumor and antimetastatic effects of native-type, glycosylated recombinant lymphotoxin (LT) on human and murine tumors transplanted in mice. The results reported here are as follows: (a) The in vivo antitumor spectrum of LT is not coincident with the in vitro study, and it has a wide antitumor spectrum and substantially inhibits the growth of human solid tumors, (b) When both syngeneic and nude mice are transplanted with Meth A tumor, the significant growth-inhibitory effect of LT is obtained in syngeneic mice, but the effect is quite small in nude mice regardless of the routes; LT attains the same degree of effectiveness as that in syngeneic mice, but at an 8 to 16 times higher dose. Furthermore, the pretreatment with anti-asialo-GM1 antibody inhibits the antitumor effects of LT in syngeneic mice, (c) In the pulmonary metastasis model induced by i.v. injection of Meth A cells, a high preventive effect of LT is obtained by systemic administration in syngeneic mice, but not in nude mice. In addition, the pretreatment with anti-asialo-GM1 antibody completely prevents the antimetastatic effect of LT, but also blocks that effect of control mice without LT treatment. In conclusion, LT appears to be a potent cytokine against tumor growth and metastasis in vivo. The differences between nude and syngeneic mice suggest the involvement of host immunity in the expression of LT function.

We have examined the pharmacokinetics of glycosylated recombinant human lymphotoxin (LT) after intravenous bolus injection in rats and compared them with those of tumor necrosis factor (TNF) or LT species. The results are as follows. 1) The mean half-life of glycosylated LT in serum increases for each increase in dose, and the distribution volume (V) and total body clearance [(Cl (total)] tend to decrease for increase in dose. On the other hand, the half-life of TNF also increases for increase in dose, but the V tends to increase for increase in dose and Cl (total) does not change. 2) The glycosylated LT distributes to all organs so far tested except brain, and tends to accumulate to kidney more than other tissues at 6 h after the injection. 3) Nonglycosylated LT produced by E. coli and the glycosylated LT species carrying both N-type and mucin-type sugar moieties (25 kDa LT) have shorter half-lives and higher Cl (total)s than 23 kDa LT carrying N-type sugar moieties alone. The 21 kDa LT, the same species as 23 kDa LT except that it lacks 15 amino acid residues at the N-terminus, disappears much faster than 23 kDa LT and shows higher V and Cl (total). Thus, glycosylated LT shows nonlinear pharmacokinetics like TNF, but the deposition is quite different from that of TNF. The high serum concentration of glycosylated LT depends upon the presence of N-type sugar moieties, but not mucin-type sugar moieties. The N-terminal protein chain of LT also correlates with the serum concentration.