Biomedical subjects

C Fukaya

Publications and source records attributed to C Fukaya.

At least 19 recordsLinked to original sources

PubMed2005

DBS therapy for the vegetative state and minimally conscious state.

Twenty-one cases of a vegetative state (VS) and 5 cases of a minimally conscious state (MCS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically at 3 months after brain injury. These cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The mesencephalic reticular formation was selected as a target in 2 cases of VS, and the CM-pf complex was selected as a target in the other 19 cases of VS and 5 cases of MCS. Eight of the 21 patients emerged from the VS, and became able to obey verbal commands. However, they remained in a bedridden state except for 1 case. Four of the 5 MCS patients emerged from the bedridden state, and were able to enjoy their life in their own home. DBS therapy may be useful for allowing patients to emerge from the VS, if the candidates are selected according to appropriate neurophysiological criteria. Also, a special neurorehabilitation system may be necessary for emergence from the bedridden state in the treatment of VS patients. Further, DBS therapy is useful in MCS patients to achieve consistent discernible behavioral evidence of consciousness, and emergence from the bedridden state.

Adolescent↗

PubMed2003

BOLD functional MRI may overlook activation areas in the damaged brain.

Clinical applications of blood-oxygenation-level-dependent contrast functional MRI (BOLD-fMRI) have been rapidly moving toward routine non-invasive cortical mapping in the patients with brain disorders. However, it is not yet clear whether the damaged brain shows same cerebral blood oxygenation (CBO) changes during neuronal activation as those in the normal adult. We compared the activation mapping obtained by BOLD-fMRI and the evoked-CBO changes measured by near infrared spectroscopy (NIRS) in normal adults (6 cases) and patients with damaged brain (6 cases of cerebral ischemia and 10 cases of brain tumors in or adjacent to the motor cortex). BOLD-fMRI demonstrated robust activation areas in the primary sensorimotor cortex (PSMC) during contralateral hand grasping tasks in all of the normal adults; however, in the cerebral ischemia (6 cases) and the brain tumors (2 cases), BOLD-fMRI demonstrated only limited activation areas in the PSMC on the lesion side during the task. NIRS demonstrated an increase of focal concentration of oxyhemoglobin and total hemoglobin at the PSMC during the task in all of the normal adults and the patients, indicating the presence of rCBF increase in response to neuronal activation. A focal concentration of deoxyhemoglobin decreased during the task in the normal adults, however, in the patients that showed limited activation areas by BOLD-fMRI, deoxyhemoglobin concentrations increased during the entire course of the task. In summary, the evoked-CBO changes occurring in the damaged brain differed from those in the normal brain. This indicates that BOLD-fMRI may overlook activation areas in the damaged brain.

Brain Ischemia↗

PubMed2003

Impairment of motor function after frontal lobe resection with preservation of the primary motor cortex.

We investigated the clinical course and characteristics of the motor deficits in patients who underwent surgical resection of the frontal lobe for tumorous lesions. Only patients who met the following criteria were included in the present study: 1) postoperative MRI revealed that resection of the frontal lobe involved the area closely adjacent to the primary motor cortex, but 2) the D wave of the corticospinal MEP did not decrease in amplitude below 50% of the original level during surgery. The extent of resection was classified into 4 groups. In Group A (6 cases), resection was limited within the area above the superior frontal sulcus and posterior to a line vertical to the line connecting the anterior and posterior commissures at the anterior commissure (AC vertical line). Resection was extended anterior to the AC vertical line in Group B (4 cases) or below the superior frontal sulcus in Group C (5 cases). In Group D (3 cases), resection was extended to both of these two boundaries. Severe motor paresis and/or apraxia of the upper and lower extremities were noted in all patients of Group D immediately after surgery. A complete recovery in the lower extremity was observed in these patients, while disturbance in the fine movements of the upper extremity remained for more than 1 year after the surgery. Disturbance in the fine movements and/or apraxia of the upper extremity were observed immediately after surgery in 2 of the Group A patients (33%), 2 of the Group B patients (50%) and 3 of the Group C patients (60%). However, a rapid recovery occurred in these patients, and only a subtle or mild disturbance remained for more than 1 year after the surgery in one of the Group B and one of the Group C patients. Permanent and severe motor deficit is rarely induced when resection of the frontal lobe is limited to only the SMA proper (corresponding roughly to Group A), the SMA proper and pre-SMA (corresponding roughly to Group B), or the SMA proper and premotor cortex (corresponding roughly to Group C), insofar as the primary motor cortex is preserved. Disturbance in fine movements of the upper extremity is frequently induced for the long term when wide areas of the SMA proper, pre-SMA as well as premotor cortex are resected altogether (corresponding roughly to Group D).

Adult↗

PubMed2003

Deep brain and motor cortex stimulation for post-stroke movement disorders and post-stroke pain.

Our experience of deep brain stimulation (DBS) and motor cortex stimulation (MCS) in patients with post-stroke movement disorders and post-stroke pain is reviewed. DBS of the thalamic nuclei ventralis oralis posterior et intermedius proved to be useful in more than 70% of patients with post-stroke involuntary movements (hemiballismus, hemichoreo-athetosis, distal resting and/or action tremor, and proximal postural tremor). The effect of DBS of the thalamic nucleus ventralis caudalis or internal capsule on post-stroke pain was usually disappointing. Excellent pain control can be achieved by MCS in approximately 50% of patients with post-stroke pain. In the course of clinical trials on MCS for the control of post-stroke pain, it was found that co-existent post-stroke involuntary movements (hemichoreo-athetosis and resting tremor) could also be controlled by MCS. Post-stroke involuntary movements, especially those in thalamic syndrome, are sometimes associated with post-stroke pain. In such disorders, involuntary movements are attenuated, but the pain in the same patients is often exacerbated by DBS of the thalamic nuclei ventralis oralis posterior et intermedius. MCS could be the therapy of choice under such circumstances. Subjective improvement of voluntary motor performance, which had been impaired in association with mild or moderate hemiparesis, was reported during MCS by approximately 20% of patients with post-stroke pain. Such an effect on voluntary motor performance appears to be caused by an inhibition of their rigidity. The reversibility of DBS and MCS makes them an important option for the control of post-stroke movement disorders and post-stroke pain.

Electrodes, Implanted↗

PubMed2003

Chronic stimulation of the globus pallidus internus for control of primary generalized dystonia.

Our experience of deep brain stimulation of the globus pallidus internus (GPi-DBS) for dystonia is summarized. A total of 5 patients with primary generalized dystonia underwent GPi-DBS. There were 3 males and 2 females. The age at onset of dystonia ranged from 8 to 45 years and the age at surgery for GPi-DBS ranged from 17 to 59 years. Two of the patients had been treated previously by bilateral thalamotomy or unilateral pallidotomy at other clinics and then developed new symptoms or recurrence. All were stimulated bilaterally. No surgical complications were encountered. The symptoms of dystonia were scored by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). The scores ranged from 18 to 62 before surgery. An improvement in the symptoms of dystonia was observed soon after the initiation of GPi-DBS, and additional progressive improvement was noted during a period of months or even years after surgery. The score at 6 months after surgery reached a level ranging from 4 to 23. The improvement in score ranged from -51% to -92%. GPi-DBS produced a marked effect even in patients who had previously undergone thalamotomy or pallidotomy. At 6 months after surgery, all patients were receiving bipolar stimulation with a wide interpolar distance, using contact 0 or 1 as the cathode and contact 2 or 3 as the anode. Stimulation was being performed at an intensity of around 2.0 V with a pulse width of 0.21 ms at a high frequency ranging from 120 to 140 Hz. GPi-DBS represents an important therapeutic option in many patients with primary generalized dystonia.

Adolescent↗

PubMed2003

Localization of thalamic cells with tremor-frequency activity in Parkinson's disease and essential tremor.

It has been reported that parkinsonian and essential tremor can be controlled by deep brain stimulation or radiofrequency lesion within the cluster of cells with a tremor-frequency activity in the ventral thalamic nuclei. However, there have been very few reports about the exact localization of cells with tremor-frequency activity in the ventral thalamic nuclei. In the present study, we investigated the localization of cells with tremor-frequency activity in the ventral thalamic nuclei employing autopower spectrum and coherence analysis. Activity of a total of 130 cells, 63 in patients with parkinsonian tremor and 67 in patients with essential tremor, were recorded from the area anterior to the nucleus ventralis caudalis. Among these cells, 31 cells showed a coherence of greater than 0.4 to the electromyographic activity of both agonist and antagonist muscles. The proportion of cells exhibiting tremor-frequency activity were 26.8% in the nucleus ventralis intermedius (Vim) and 25.0% in the nuclei ventralis oralis posterior et anterior (Vop + Voa). There were no significant differences in proportion by nuclear location or disease. The present study demonstrated that cells with tremor-frequency activity are widely distributed over the area extending from the Vim to the Vop + Voa. This indicates that the best location for placing electrodes for deep brain stimulation or a radiofrequency lesion cannot be defined by identification of cells with tremor-frequency activity alone.

Action Potentials↗

PubMed2003

DBS therapy for a persistent vegetative state: ten years follow-up results.

Twenty-one cases of a persistent vegetative state (PVS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically at 3 months after the brain injury. The 21 cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The stimulation sites were the mesencephalic reticular formation (2 cases) and CM-pf complex (19 cases). Eight of the patients emerged from the PVS, and became able to obey verbal commands. However, they remained in a bedridden state. These 8 cases revealed a desynchronization on continuous EEG frequency analysis. The Vth wave of the ABR and N20 of the SEP could be recorded even with a prolonged latency, and the pain-related P250 was recorded with an amplitude of over 7 microV. The mean survival time of these 8 cases was 6.1 years, as compared to 3.1 years for the other 13 cases. Overall, 4 cases are alive after more than 10 years. DBS therapy may be useful for allowing patients to emerge from a PVS, if the candidates are selected according to neurophysiological criteria. The fact that 19% (4/21) of the PVS cases treated with DBS survived for over 10 years should be stressed in comparison with the usual survival period for the untreated PVS.

Adult↗

PubMed2002

Deep brain stimulation therapy for a persistent vegetative state.

Twenty cases of a persistent vegetative state (PVS) caused by various kinds of brain damage were neurologically and electrophysiologically evaluated at 3 months after persistence of the PVS, and were treated by deep brain stimulation (DBS) therapy. The stimulation sites were the mesencephalic reticular formation (2 cases) and CM-pf complex (18 cases). Seven of the patients emerged from the PVS, and became able to obey verbal commands. However, they remained in a bedridden state. These 7 cases revealed a desynchronization or slight desynchronization pattern on continuous EEG frequency analysis. The Vth wave of ABR and N20 of SEP could be recorded even with a prolonged latency, and the pain-related P250 was recorded with an amplitude of over 7 microV. We conclude that chronic DBS therapy may be useful for allowing the patient to emerge from a PVS, if the candidates are selected according to the neurophysiological criteria. In view of the severely disabled state of the patients who emerged from the PVS, a special rehabilitation program which includes neurostimulation therapy may be necessary for treatment of the PVS.

Adult↗

PubMed2002

Control of post-stroke movement disorders using chronic motor cortex stimulation.

The effects of motor cortex (MC) stimulation on post-stroke movement disorders were analyzed in 50 patients. These individuals either underwent MC stimulation primarily for the purpose of controlling their post-stroke involuntary movements (n = 8) or underwent MC stimulation for the purpose of controlling their post-stroke central pain (n = 42). In the latter patients, the effects of MC stimulation on co-existent involuntary or voluntary movement disorders were analyzed retrospectively. Good control of involuntary movements was observed in 2 of 3 patients with hemichoreo-athetosis, 2 of 2 patients with distal resting or action tremor, and 1 of 3 patients with proximal postural tremor. Subjective improvements in motor performance were reported by 8 patients who had mild motor weakness, and the effects appeared to be attributable to attenuation of rigidity. We consider that these findings justify further clinical studies on MC stimulation for the control of post-stroke movement disorders.

Electric Stimulation Therapy↗

PubMed2002

Increase in focal concentration of deoxyhaemoglobin during neuronal activity in cerebral ischaemic patients.

BACKGROUND AND PURPOSE: Blood oxygenation level dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been applied to functional mapping in brain disorders, based on the assumption that normal adults and patients with brain disorders exhibit similar evoked cerebral blood oxygenation (CBO) changes. This study compared evoked CBO changes measured by near infrared spectroscopy (NIRS) with the activation mapping obtained by BOLD-fMRI in patients with cerebral ischaemia. METHODS: The study involved six normal adults and six patients with cerebral ischaemia. Hand grasping was performed as a motor task. All patients could perform the task similarly to the controls at the time of examination, but single photon emission computed tomography demonstrated low baseline cerebral blood flow and a decreased haemodynamic reserve in the primary sensorimotor cortex on the lesion side. Using NIRS, concentration changes of deoxyhaemoglobin (Deoxy-Hb), oxyhaemoglobin (Oxy-Hb), and total haemoglobin (Total-Hb) were measured in the primary sensorimotor cortex contralateral to the task. BOLD-fMRI signals were measured by 1.5 T magnetic resonance imaging using an echo-planar technique. Activation maps were calculated by statistical parametric mapping. RESULTS: In the controls, Deoxy-Hb decreased in association with increases of Oxy-Hb and Total-Hb in the primary sensorimotor cortex during the task. However, in the patients, Deoxy-Hb increased significantly from baseline, while Oxy-Hb and Total-Hb also increased, indicating the presence of rCBF increases in response to neuronal activation. BOLD-fMRI demonstrated only limited activation areas in the primary sensorimotor cortex on the lesion side. CONCLUSION: The CBO changes in patients with cerebral ischaemia differed from those of normal adults; Deoxy-Hb was increased in activation areas of the patients. This implies that BOLD-fMRI may overlook activation areas in the patients unless both increases and decreases of signal are taken into consideration.

Adult↗

PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic alpha-keto heterocycles as novel inhibitors of human chymase.

We designed nonpeptidic chymase inhibitors based on the structure of a peptidic compound (1) and demonstrated that the combination of a pyrimidinone skeleton as a P3-P2 scaffold and heterocycles as P1 carbonyl-activating groups can function as a nonpeptidic chymase inhibitor. In particular, introduction of heterobicycles such as benzoxazole resulted in more potent chymase-inhibitory activity. Detailed structure-activity relationship studies on the benzoxazole moiety and substituents at the 2-position of the pyrimidinone ring revealed that 2r (Y-40079) had the most potent chymase-inhibitory activity (K(i) = 4.85 nM). This compound was also effective toward chymases of nonhuman origin and showed good selectivity for chymases over other proteases. Pharmacokinetic studies in rats indicated that 2r was absorbed slowly after oral administration and showed satisfactory bioavailability (BA) (T(max) = 6.0 +/- 2.3 h, BA = 19.3 +/- 6.6%, t(1/2) = 35.7 +/- 13.3 h). In conclusion, 2r is a novel, potent, and orally active chymase inhibitor which would be a useful tool in elucidating the pathophysiological roles of chymase.

Animals↗

PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.

Potent human chymase inhibitors with high enzymatic selectivity and satisfactory metabolic stability were obtained by replacing the Val-Pro (P3-P2) dipeptide portion of the previously described inhibitor 1 with a nonpeptidic pyrimidinone skeleton. The potency of the novel compounds was further enhanced by the introduction of carbamoyl-substituted difluoromethylene ketone moieties. The most potent chymase inhibitor of the newly created series was 2u (Y-40018), which had a K(i) of 2.62 nM. Compound 2u possessed high selectivity for human chymase since it lacked significant activity toward other representative human proteolytic enzymes. Moreover its strict specificity for human chymase suggested that 2u strongly inhibited human and canine chymases but not rat and mouse ones. Pharmacokinetic studies in rats and dogs indicated that 2u was absorbed rapidly after oral administration and had satisfactory bioavailability in these experimental animal species (rat, 17%; dog, 32%). In conclusion, 2u is a novel, potent, and orally active chymase inhibitor which would prove very useful in revealing the precise roles of the latter in various pathophysiological processes.

Animals↗

PubMed2001

Non-peptidic inhibitors of human chymase. Synthesis, structure-activity relationships, and pharmacokinetic profiles of a series of 5-amino-6-oxo-1,6-dihydropyrimidine-containing trifluoromethyl ketones.

Chymase possesses a wide variety of actions, including promotion of angiotensin II production and histamine release from mast cells. However, due to a lack of effective inhibitors featuring both high inhibitory activity and high metabolic stability, the pathophysiological role of chymase has not been fully elucidated. We designed non-peptidic inhibitors based on the predicted binding mode of the peptidic chymase inhibitor Val-Pro-Phe-CF3 and demonstrated that the Val-Pro unit is replaceable with a (5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidinyl)acetyl moiety. Structure-activity relationship studies revealed that phenyl substitution at the 2-position of the pyrimidinone ring is indispensable for high activity. The most potent compound 1h (Ki = 0.0506 microM) is superior in potency to the parent peptidic inhibitor Val-Pro-Phe-CF3 and has good selectivity for chymase over other proteases. The related analogue 1e was orally absorbed and maintained high plasma levels for at least 2h. These results suggest that the derivatives reported here could be developed as agents for treatment of chymase-induced disease.

Animals↗

PubMed2001

Intraoperative wake-up procedure with propofol and laryngeal mask for optimal excision of brain tumour in eloquent areas.

This is the first thesis describing a new technique for awake craniotomy using a laryngeal mask. Awake craniotomy with propofol infusion has become increasingly popular for the optimal excision of brain tumours located in eloquent areas. During awake craniotomy, tracheal intubation is not performed and propofol infusion is limited to within doses which render the patient just sedated. This asleep-awake procedure is occasionally associated with difficulty in controlling brain volume, especially in patients with a significant mass effect of their brain tumours, since sufficient sedation with propofol tends to cause hypercapnea. We report an intraoperative wake-up procedure employing a laryngeal mask, which enables general anaesthesia to be performed at a sufficient dose of propofol and with control of the brain volume under mechanically assisted ventilation. Before the beginning of cortical mapping, propofol infusion is completely terminated, so allowing the patient to wake up within 5-15 min. Following completion of the tumour excision, general anaesthesia is re-induced at a sufficient dose of propofol. The laryngeal mask can be temporarily removed and repositioned with ease, if necessary. In our experience, this technique is applicable for the optimal excision of brain tumours, especially in patients who are very obese or those who have very large lesions.

Anesthetics, Intravenous↗

PubMed2001

Motor cortex stimulation for phantom limb pain: comprehensive therapy with spinal cord and thalamic stimulation.

The effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) were analyzed in 19 patients with phantom limb pain. All of the patients underwent SCS and, if the SCS failed to reduce the pain, the patients were considered for DBS and/or MCS. Satisfactory pain control for the long-term was achieved in 6 of 19 (32%) by SCS, 6 of 10 (60%) by DBS and 1 (20%) of 5 by MCS. SCS and DBS of the VC sometimes produced a dramatic effect on the pain, leading to a long pain-free interval and infrequent use of stimulation. The effects of both DBS of the VC and MCS were tested in four. One patient of them reported better pain control by MCS than by DBS, whereas two reported the opposite results. There is no evidence at present for an advantage of MCS over SCS and DBS of the VC in controlling phantom limb pain.

Adult↗

PubMed2001

Motor cortex stimulation for post-stroke pain: comparison of spinal cord and thalamic stimulation.

We analyzed the effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) in 45 patients with post-stroke pain. Satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels (7% by SCS, 25% by DBS and 48% by MCS). A painful sensation was sometimes produced by stimulation of the VC as well as the post-central, pre-central and pre-frontal cortices. Such a sensation occurred less frequently as the stimulation site was moved to higher levels (50% at the VC, 39% at the post-central cortex, 6% at the pre-central cortex and 3% at the pre-frontal cortex). These findings imply that abnormal processing of nociceptive information develops at the level of deafferentation and spreads to higher levels to a varying extent. This may be one of the reasons why satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels.

Analgesia↗

PubMed2001

Subthalamic nucleus stimulation for Parkinson disease: benefits observed in levodopa-intolerant patients.

OBJECT: A blinded evaluation of the effects of subthalamic nucleus (STN) stimulation was performed in levodopa-intolerant patients with Parkinson disease (PD). These patients (Group I, seven patients) were moderately or severely disabled (Hoehn and Yahr Stages III-V during the off period), but were receiving only a small dose of medication (levodopa-equivalent dose [LED] 0-400 mg/day) because they suffered unbearable side effects. The results were analyzed in comparison with those obtained in patients with advanced PD (Group II, seven patients) who were severely disabled (Hoehn and Yahr Stages IV and V during the off period), but were treated with a large dose of medication (500-990 mg/day). METHODS: The patients were evaluated twice at 6 to 8 months after surgery. To determine the actual benefits afforded by STN stimulation to their overall daily activities, the patients were maintained on their medication regimen with optimal doses and schedules. Stimulation was turned off overnight for at least 12 hours. It was turned on in the morning (or remained turned off), and each patient's best and worst scores on the Unified Parkinson's Disease Rating Scale during waking daytime activity were recorded as on- and off-period scores, respectively. The order of assessment with respect to whether stimulation was occurring was determined randomly. The STN stimulation markedly improved daily activity and total motor scores in Group I patients. The percentage time of immobility (Hoehn and Yahr Stages IV and V) became 0% in patients who were intermittently immobile while not receiving stimulation. Improvements were demonstrated in tremor, rigidity. akinesia, and gait subscores. The STN stimulation produced less marked but still noticeable improvements in the daily activity and total motor scores in Group II patients. The percentage time of immobility as well as the LED was reduced in patients who displayed intermittent immobility with pronounced motor fluctuations while not receiving stimulation. Improvements were demonstrated in tremor, rigidity, and dyskinesia subscores in these patients. In contrast, STN stimulation did not improve the overall daily activities at all in patients who had become unresponsive to a tolerable dose of levodopa and were continuously immobile, even though these patients' tremor and rigidity subscores were still improved by stimulation. CONCLUSIONS: Consistent with earlier findings, the great benefit of STN stimulation in levodopa-intolerant patients is that STN stimulation can reduce the level of required levodopa medication. This suggests that STN stimulation could be a therapeutic option for patients with less-advanced PD by allowing levodopa medication to be maintained at as low a dose as possible, and to prevent adverse reactions to the continued use of large-dose levodopa.

Adult↗

PubMed2001

New method of deep brain stimulation therapy with two electrodes implanted in parallel and side by side.

Reversibility and adaptability are preferred features of long-term therapeutic deep brain stimulation (DBS). In such therapy, a permanent stimulating electrode with four contact points is placed at the stimulation site and, generally speaking, bipolar stimulation is induced by various pairs of adjacent contact points on one electrode. The stimulation sites are thus all located along the trajectory of the implanted electrode. In a patient with unilateral severe essential tremor, the authors implanted two electrodes side by side and parallel to each other in the unilateral thalamic ventralis intermedius nucleus. Using these electrodes, the authors were able to deliver current flow not only along the electrode trajectory, but also between the two electrodes in a direction parallel to the anterior commissure-posterior commissure line. Although individual stimulations, delivered by each of the two electrodes using all parameters and all stimulation points, were unable to stop the patient's tremor completely without adverse effects, the new stimulation method, in which electrical currents passed between the two electrodes, effected complete abolition of the tremor without adverse effects. With the aid of this method, one can use two electrodes, implanted in parallel and side by side, to achieve maximum efficacy and to reduce adverse effects in some instances of DBS therapy.

Aged↗