Erythromelalgia associated with Clitocybe acromelalga intoxication.

CONTEXT: Erythromelalgia is a rare disorder characterized by reddening, severe burning pain, and swelling of the extremities. Food poisoning by Clitocybe acromelalga, a poisonous mushroom, is known to induce erythromelalgia; however, its treatment protocol remains unclear. We describe here three cases of erythromelalgia following the consumption of C. acromelalga with varying clinical courses. CASE DETAILS: Of the three patients, the first patient presented 22 days after the onset of erythromelalgia; although he was treated with aspirin, numbness in the limbs persisted as sequela. Patient 2 presented at 3 days after the symptomatic onset and was immediately treated with high-dose intravenous nicotinic acid, with a dramatic symptomatic improvement. Patient 3, who had milder symptoms, spontaneously recovered within a week without any treatment. DISCUSSION: The clinical manifestations and varying clinical courses associated with C. acromelalga toxicity are discussed here, with the pathogenesis of this mycotoxin and a potential treatment. Detailed interviews of such patients are important, particularly because of the remarkably slow course of this mycotoxin as compared with common food poisonings. Treatment with intravenous nicotinic acid was associated with improvement in one patient. We believe that this painful disorder might thus be treatable, although the mechanism underlying the treatment remains unclear.

Effect of transcranial magnetic stimulation on P300 of event-related potential.

When the odd stimulation is presented, the positive component of electroencephalograph is induced at around 300 ms after the odd stimulation. This positive component is called P300. Many studies suggest that P300 may result from the summation of activity from multiple generators located in widespread cortical and subcortical areas. However, there is still no conclusive indication of the sources of P300. In this paper, we focus on the left supramaginal gyrus as one of the sources of P300. We investigated the temporal aspect of this area using TMS (transcranial magnetic stimulation). We investigated the relationship between the latency of the P300 and an effect of TMS when the left supramarginal gyrus was stimulated by TMS. In our previous study, we reported a method of removing stimulus artifact during TMS with Sample-and-Hold circuit and electroencephalogram (EEG) activity evoked by TMS could be measured successfully. In addition to this method, independent component analysis (ICA) was also applied to recorded EEG data in order to remove the stimulus artifact by off-line analysis. By using these methods, short latency (< 15 ms) EEG responses to TMS could be obtained. We stimulated the left supramarginal gyrus using a figure-eight coil during auditory oddball task. The TMS at 150 ms and 200 ms after the oddball sounds were presented. When the TMS was applied at 200 ms after the oddball stimulation, the peak response of P300 was delayed around 50 ms. Difference of the peak latency between the control measurement and the case of TMS applying at 150 ms was not significant. However, the differences of the peak latency of the control measurement and the peak latency of the measurement in the cases of TMS applying at 200 ms and 250 ms was significant (p<0.05). We considered that this delay was due to inhibiting to recognize the target stimulation.

Feed-forward control of post-stroke movement disorders by on-demand type stimulation of the thalamus and motor cortex.

Deep brain stimulation (DBS) of the thalamus (Vo/Vim) has become popular as a means of controlling involuntary movements, including post-stroke movement disorders. We have also found that post-stroke movement disorders and motor weakness can sometimes be controlled by motor cortex stimulation (MCS). In some forms of movement disorders, motor dysfunction becomes evident only when patients intend to move their body. We have developed an on-demand type stimulation system which triggers stimulation by detecting intrinsic signals of intention to move. Such a system represents feed-forward control (FFC) of involuntary movements. We report here our experience of DBS and MCS for controlling post-stroke movement disorders, and discuss the value of FFC. Excellent control of post-stroke movement disorders was achieved by conventional DBS and/or MCS in 20 of 28 patients with hemichoreoathetosis, hemiballism tremor, and motor weakness. FFC was tested in 6 patients who demonstrated excellent control of post-stroke postural tremor or motor weakness by conventional DBS or MCS. The on-demand stimulation provided satisfactory FFC in 4 of 4 patients with postural tremor and 2 of 2 patients with motor weakness, when the activity of muscles involved in posturing or intention to move was fed into the system. These findings justify further clinical studies on DBS and MCS in patients with post-stroke movement disorders. The on-demand type stimulation system may also be useful for overcoming various post-stroke movement disorders.

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.

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.

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.

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.

[Preoperative autologous blood donation in patients undergoing open heart surgery].

We examined the possibility to avoid the homologous blood transfusion in patients undergoing open heart surgery by predonation of 200 ml or 400 ml on the day before operation. Between March 1999 and December 2001, 117 patients underwent scheduled open heart surgery. In these patients, preoperatively collected autologous blood on the day before operation amounted 200 ml or 400 ml. We divided these patients into 3 groups according to the necessity of homologous blood, no transfusion (group A, n = 77), intraoperative transfusion (group B 1, n-29) and postoperative transfusion (group B 2, n = 11). In 65.8% of patients the homologous blood transfusion could be avoided. Preoperative, intraoperative and postoperative factors were compared in the 3 groups. Especially, old age, female, body weight and preoperative hemoglobin value were significantly different between 3 groups. Postoperative Svo2 and postoperative hemoglobin value were significantly different between 3 groups. The purpose of this study was to evaluate that the predonation of 200 ml or 400 ml on the day before operation may be to avoid the homologous blood transfusion and that preoperative, intraoperative and postoperative factors in regard to homologous blood transfusion.

The characteristics of the bacterial community structure and population dynamics for phosphorus removal in SBR activated sludge processes.

The characteristics of the bacterial community structure and population dynamics for phosphorus removal in activated sludge were investigated using laboratory-scale sequencing batch reactor (SBR) activated sludge processes fed with four different carbon sources. Phosphorus removal activity, quinone profile of the activated sludge and isolated bacterial strains were monitored. An enhanced phosphorus removal activity was accompanied by the increase in ubiquinone-9 (Q-9). The relationships between phosphorus removal activity and Q-9 contents of the isolated bacterial strains were dependent neither on the organic substrates nor on the species of isolated bacterial strains. The enhanced phosphorus removal capability of activated sludge seemed to be due to the increase in the populations of bacteria with activity of phosphorus removal, i.e. species succession of bacteria in activated sludge ecosystems, rather than the increase in the phosphorus removal capability of phosphorus removal bacteria. Not only Acinetobacter but also Pseudomonas identified from isolated strains were regarded as representative polyphosphates-accumulating organisms and predominant species to the whole of bacterial population in activated sludge for phosphorus removal.

Expression of a gene for Mn-peroxidase from Coriolus versicolor in transgenic tobacco generates potential tools for phytoremediation.

In efforts aimed at the detoxification of contaminated areas, plants have many advantages over bacteria and fungi. We are attempting to enhance the environmental decontamination functions of plants by transferring relevant genes from microorganisms. When the gene for Mn-peroxidase (MnP) from Coriolus versicolor was expressed in transgenic tobacco plants, one line (designated fMnP21) expressed MnP activity at levels 54-fold higher than in control lines. When undamaged roots of transgenic plants were applied to liquid medium supplemented with 250 microM pentachlorophenol (PCP), the decrease in the level of PCP in fMnP21 (86% reduction) was about 2-fold higher than that in control lines (38% reduction). Expression of the gene for MnP in the transgenic plants had no obvious negative effects on their vegetative and sexual growth. Our system should contribute to the development of novel methods for the removal of hazardous chemicals from contaminated environments using transgenic plants.

[Blood conservation in thoracic aortic surgery with total cardiopulmonary bypass].

BACKGROUND: In thoracic aortic surgery, a large number of homologous transfusions sometimes cause systemic inflammatory response, which may lead to pulmonary dysfunction, renal dysfunction and brain edema. To predict the need for homologous blood transfusion in aortic surgery, we use blood transfusion index (preoperative Ht x body weight) to predict the magnitude of homologous transfusion. PATIENTS AND METHODS: From Dec 1997 to May 2000, 59 consecutive patients were underwent thoracic aortic graft replacement with total cardiopulmonary bypass. These patients were divided in 2 groups, who were underwent graft replacement without blood transfusions, and who needed blood transfusions. Each group was compared in age, sex, emergency, Ht, CPB time, blood transfusion index and operative mortality. RESULTS: Forty patients (67.7%) did not required blood transfusion. In elective cases (32 cases), 84.3% were underwent operation without blood transfusion. There was no significant difference between 2 groups in terms of age and mean bypass duration. Blood transfusion index was significantly higher in transfusion group (2,320 +/- 784) compared with that in not transfusion group (1,445 +/- 706). CONCLUSION: Blood transfusion index was useful preoperative parameter to predict the need for homologous transfusion.

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.

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.

Tea catechin, (-)-epigallocatechin gallate, causes membrane depolarizations of myenteric neurons in the guinea-pig small intestine.

Intracellular recordings were made from enteric neurons in the myenteric plexus of the guinea-pig small intestine to examine actions of one of tea catechins, (-)-epigallocatechin gallate (EGCG), on neuronal activity. EGCG at concentrations from 1 to 20 microM depolarized about 60% of both of S and AH neurons in a concentration-dependent manner, although EGCG-induced depolarizations were largely varied in amplitude from neuron to neuron. The depolarizations started passing off during the presence of EGCG at higher concentrations, and became smaller or almost abolished with repeated applications, indicating the EGCG-induced response shows desensitization-like characteristics. The EGCG-depolarization was associated with a decrease in input membrane resistance, and their reversal potential was estimated about -30 mV. Since the EGCG-depolarization was recorded in the absence of external Ca(2+), it is concluded that one of tea catechins has direct depolarizing effects on a population of myenteric neurons.

Delayed administration of JTP-2942, a novel thyrotropin-releasing hormone analogue, improves cerebral blood flow and metabolism in rat postischaemic brain.

1. The aim of the present study was to examine the central nervous system action of JTP-2942, a novel thyrotropin-releasing hormone (TRH) analogue, from the point of view of cerebral blood flow (CBF) and metabolism in the postischaemic brain. 2. Left middle cerebral artery ischaemia was induced for 90 min followed by reperfusion. 3. Animals were separated into four groups: (i) low-dose (0.003 mg/kg) JTP-2942; (ii) high-dose (0.03 mg/kg) JTP-2942; (iii) cystidine diphosphate choline (500 mg/kg); and (iv) saline. The test drug or saline was administered intravenously 1 week after ischaemia. 4. Local CBF and local cerebral glucose utilization were measured autoradiographically, adjacent sections were stained with haematoxylin-eosin and infarction size was measured. 5. JTP-2942 ameliorated the reduction of local CBF and glucose utilization except in the ischaemic core. In particular, the higher dose (0.03 mg/kg) of JTP-2942 significantly increased local CBF and glucose utilization not only in peri-infarcted areas, but also in distal and contralateral areas. 6. These results suggest that JTP-2942 treatment may be beneficial for improving cerebral circulation and metabolism in the postischaemic brain.

[Deep brain stimulation therapy for involuntary movements].

During the last decade, it has become clear that deep brain stimulation (DBS) therapy provides a dramatic improvement in the symptoms of movement disorders. We have experienced DBS in 110 patients with various types of involuntary movements, and confirmed the benefits of stimulation of the thalamic nucleus ventralis intermedius (Vim), internal globus pallidus (GPi) and subthalamic nucleus (STN) in these patients. DBS therapy affords the best effect on tremor when the Vim is selected as the stimulation site. DBS therapy is also useful for controlling rigidity when the GPi or STN is stimulated. Improvements of bradykinesia and gait disturbance are often induced by DBS therapy involving the GPi or STN. Dopa-induced dyskinesia can be attenuated effectively by the direct and/or indirect effects of DBS therapy. DBS of the Vim also provides excellent control of post-stroke involuntary movements, including hemiballism and hemichoreoathetosis. Dystonia in young patients is controlled effectively by DBS of GPi. Ablative procedures for control of involuntary movement disorders, such as thalamotomy and pallidotomy, always carry a risk associated with creating additional lesions in an already damaged brain. In contrast, there is not such a risk in DBS therapy. This modality of therapy is an important option in treating involuntary movements.

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.

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.

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.

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.