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Shunsuke Nomura, Akitsugu Kawashima, Hiroyuki Akagawa and Takakazu Kawamata

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Takakazu Kawamata, John W. Peterson, Takao Bun and Nicholas T. Zervas

✓ Although phorbol esters, synthetic activators of protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8–12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro (50–85% of maximum) in normal canine cerebral arteries. Increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar to those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6–8% of total PKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm.

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Taku Yoneyama, Takakazu Kawamata, Masahiko Tanaka, Koji Yamaguchi and Yoshikazu Okada

In carotid endarterectomy (CEA), the traditional retractors are often difficult to use because they tend to obstruct surgical manipulations, especially in the deep operative field on the rostral side. The authors have invented a new omnidirectional retractor-supporting ring (OD ring) to solve the problems of traditional retractors. The OD ring has an ellipsoid-shaped frame (major axis: 275 mm, minor axis: 192 mm) with 22 equally spaced outward protrusions. Rubber bands from which blunt mini-hooks are hung are twisted around the protrusions. The OD ring was placed on the operative area, and the skin edges were retracted by mini-hooks placed symmetrically. The hooks were moved gradually from the shallow to the deep operative field as surgical dissection continued to expose the carotid bifurcation and distal internal carotid artery (ICA). The OD ring was used in 158 consecutive CEAs in the authors' institute between July 2010 and October 2013. The OD ring provided a flatter surgical field and was less obstructive than traditional retractors, thereby facilitating surgical manipulation in the deep operative field such as at the distal ICA. Furthermore, because of its simpler shape, angiorrhaphy could be conducted more smoothly, with less tangled thread during closure of the arteriotomy. There were no technical complications related to the OD ring. As a new retractor system for CEA, the OD ring is less obstructive and provides a flatter surgical field than traditional retractors, thereby facilitating surgical manipulations in the deep operative field around the distal ICA.

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Shiro Horisawa, Takashi Arai, Naoki Suzuki, Takakazu Kawamata and Takaomi Taira

Cerebellar neuromodulation could influence the pathological abnormalities of movement disorders through several connections between the cerebellum and the basal ganglia or other cortices. In the present report, the authors demonstrate the effects of cerebellar deep brain stimulation (DBS) on a patient with severe generalized fixed dystonia (FD) that was refractory to bilateral pallidotomy and intrathecal baclofen therapy. A previously healthy 16-year-old girl presented with generalized FD. Bilateral pallidotomy and intrathecal baclofen therapy had failed to resolve her condition, following which she received DBS through the bilateral superior cerebellar peduncle (SCP) and dentate nucleus (DN). Ipsilateral stimulation of the SCP or DN improved the FD, and the ability of DBS administered via the SCP to relax muscles was better than that of DN DBS. A considerable improvement of generalized FD, from a bedridden state to a wheelchair-bound state, was observed in the patient following 6 months of chronic bilateral DBS via the SCP; moreover, the patient was able to move her arms and legs. The findings in the present case suggest that neuromodulation of deep cerebellar structures is a promising treatment for FD that is refractory to conventional treatments.

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Shiro Horisawa, Mieko Oka, Kotaro Kohara, Takakazu Kawamata and Takaomi Taira

Camptocormia is a rare, involuntary movement disorder, presenting as truncal flexion while standing or walking, and is mainly observed as a feature of Parkinson’s disease (PD) and primary dystonia. Deep brain stimulation (DBS) of the globus pallidus internus is effective for refractory camptocormia observed with PD or dystonia. However, the effectiveness of pallidotomy for camptocormia has not been investigated. The authors report the case of a 38-year-old man with anterior truncal bending that developed when he was 36 years old. Prior to the onset of the symptom, he had been taking antipsychotic drugs for schizophrenia. There were no features of PD; the symptom severely interfered with his walking and daily life. He was given anticholinergics, clonazepam, and botulinum toxin injections, which did not result in much success. Because of the patient’s unwillingness to undergo implantation of a hardware device, he underwent staged bilateral pallidotomy with complete resolution for a diagnosis of tardive dystonic camptocormia. The Burke-Fahn-Marsden dystonia rating scale subscore for the trunk before and after bilateral pallidotomy was 3 and 0, respectively. No perioperative adverse events were observed. Effects have persisted for 18 months. Bilateral pallidotomy can be a treatment option for medically refractory dystonic camptocormia without the need for device implantation.

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Fujun Liu, Wei Chen and Jing Chen

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Tetsuryu Mitsuyama, Takakazu Kawamata, Fumitaka Yamane, Akira Awaya and Tomokatsu Hori

Object. A synthetic heterocyclic pyrimidine compound, MS-818 (2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate) is reported to have a variety of biological activities including neurite outgrowth, astrocyte differentiation, suppression of neuronal apoptosis, regeneration of injured peripheral nerves, fracture repairs, angiogenesis, and superovulation. To be able to explicate the neurotrophic effects of MS-818, the authors evaluated its effect on the reduction of infarct volume and amelioration of sensorimotor dysfunction in a rat model of focal ischemia.

Methods. Forty male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion and assigned to one of four treatment groups (10 animals in each group). The MS-818 (1, 5, or 10 mg/kg) or phosphate-buffered saline (control group) was administered intraperitoneally at onset of ischemia and again 24 hours later. The rats were killed 48 hours after they underwent surgery to induce stroke, and infarct volume was determined using an image-analysis computer software program following staining with 2,3,5-triphenyltetrazolium chloride. Postischemic neurological deficit and body weight were also assessed.

Conclusions. Significant reductions in infarct volume (total and cortical infarction) were found in all the MS-818—treated groups compared with the control group. Furthermore, MS-818 induced significant amelioration of sensorimotor dysfunction, as indicated by the results of forelimb and hindlimb placing tests. The present findings suggest that MS-818, which has a much smaller molecular weight than neurotrophic peptides, represents a new approach to the treatment of focal cerebral ischemia.

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Hiroyuki Kurihara, Koji Yamaguchi, Tatsuya Ishikawa, Takayuki Funatsu, Go Matsuoka, Yoshihiro Omura, Yoshikazu Okada and Takakazu Kawamata

Surgical treatments for moyamoya disease (MMD) include direct revascularization procedures with proven efficacy, for example, superficial temporal artery (STA) to middle cerebral artery (MCA) bypass, STA to anterior cerebral artery bypass, occipital artery (OA) to MCA bypass, or OA to posterior cerebral artery bypass. In cases with poor development of the parietal branch of the STA, the posterior auricular artery (PAA) is often developed and can be used as the bypass donor artery. In this report, the authors describe double direct bypass performed using only the PAA as the donor in the initial surgery for MMD.

In the authors’ institution, MMD is routinely treated with an STA-MCA double bypass. Some patients, however, have poor STA development, and in these cases the PAA is used as the donor artery. The authors report the use of the PAA in the treatment of 4 MMD patients at their institution from 2013 to 2016. In all 4 cases, a double direct bypass was performed, with transposition of the PAA as the donor artery. Good patency was confirmed in all cases via intraoperative indocyanine green angiography and postoperative MRA or cerebral angiography. The mean blood flow measurement during surgery was 58 ml/min. No patients suffered a stroke after revascularization surgery.

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Shiro Horisawa, Taku Ochiai, Shinichi Goto, Takeshi Nakajima, Nobuhiko Takeda, Takakazu Kawamata and Takaomi Taira

OBJECTIVE

Meige syndrome is characterized by blepharospasm and varied subphenotypes of craniocervical dystonia. Current literature on pallidal surgery for Meige syndrome is limited to case reports and a few small-scale studies. The authors investigated the clinical outcomes of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with Meige syndrome.

METHODS

Sixteen patients who underwent GPi DBS at the Tokyo Women’s Medical University Hospital between 2002 and 2015 were included in this study. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement subscale (BFMDRS-M) scores (range 0–120) obtained at the following 3 time points were included in this analysis: before surgery, 3 months after surgery, and at the most recent follow-up evaluation.

RESULTS

The patients’ mean age (± SD) at symptom onset was 46.7 ± 10.1 years, and the mean disease duration at the time of the authors’ initial evaluation was 5.9 ± 4.1 years. In 12 patients, the initial symptom was blepharospasm, and the other 4 patients presented with cervical dystonia. The mean postoperative follow-up period was 66.6 ± 40.7 months (range 13–150 months). The mean total BFMDRS-M scores at the 3 time points were 16.3 ± 5.5, 5.5 ± 5.6 (66.3% improvement, p < 0.001), and 6.7 ± 7.3 (58.9% improvement, p < 0.001).

CONCLUSIONS

The results indicate long-term efficacy for GPi DBS for the majority of patients with Meige syndrome.

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Tomokazu Takakura, Yoshihiro Muragaki, Manabu Tamura, Takashi Maruyama, Masayuki Nitta, Chiharu Niki and Takakazu Kawamata

OBJECTIVE

The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits.

METHODS

Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (DHS-L) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between DHS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change.

RESULTS

From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (DHS-L < 10 mm, n = 6), the nonadjacent group (DHS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were correlations between DHS-L and recovery of grip strength at 1 week, 3 weeks, and 3 months after surgery (r = 0.74, 0.68, and 0.65, respectively). Postsurgical nTMS was accomplished in 13 patients. In 9 of 13 cases, nTMS-MEP from APB muscle was positive at 1 week after surgery. Excluding the case in which nTMS-MEP was negative from the presurgical nTMS study, recoveries in grip strength were compared between 2 groups, in which nTMS-MEP at 1 week after surgery was positive (n = 9) or negative (n = 3). Significant differences were observed between the 2 groups at 1 week, 3 weeks, and 3 months after surgery (p < 0.01). Positive nTMS-MEP at 1 week after surgery correlated well with the motor recovery at 1 week, 3 weeks, and 3 months after surgery (r = 0.87, 0.88, and 0.77, respectively).

CONCLUSIONS

Navigated TMS is a useful tool for identifying motor eloquent areas. The results of the present study have demonstrated the predictive value of nTMS in upper-extremity motor function recovery from postsurgical neurological deficits. The longer DHS-L and positive nTMS-MEP at 1 week after surgery have prognostic values of better recovery from postsurgical neurological deficits.