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One hundred and seven patients in vegetative state (VS) were evaluated neurologically and electrophysiologically over 3 months (90 days) after the onset of brain injury. Among these patients, 21 were treated with deep brain stimulation (DBS). The stimulation sites were the mesencephalic reticular formation (two patients) and centromedian-parafascicularis nucleus complex (19 cases). Eight of the patients recovered from VS and were able to obey verbal commands at 13 and 10 months in the case of head trauma and at 19, 14, 13, 12, 12 and 8 months in the case of vascular disease after comatose brain injury, and no patients without DBS recovered from VS spontaneously within 24 months after brain injury. The eight patients who recovered from VS showed desynchronization on continuous EEG frequency analysis. The Vth wave of the auditory brainstem response and N20 of the somatosensory evoked potential could be recorded, although with a prolonged latency, and the pain-related P250 was recorded with an amplitude of > 7 μV. Sixteen (14.9%) of the 107 VS patients satisfied these criteria in our electrophysiological evaluation, 10 of whom were treated with DBS and six of whom were not treated with DBS. In these 16 patients, the recovery rate from VS was different between the DBS therapy group and the no DBS therapy group (P < 0.01, Fisher's exact probability test) These findings indicate that DBS may be useful for the recovery of patients from VS if the candidates are selected on the basis of electrophysiological criteria.

Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

Chronic deep brain stimulation therapy has the reversibility, selectivity and adjustability needed to achieve an adequate effect, so that it represents an ideal tool for functional neurosurgery designed to treat parkinsonian symptoms. Some kinds of chronic stimulation have become an alternative to lesion-making surgery, supported by the fact that high-frequency stimulation induces quite a small area of inactivity around the stimulating electrode compared with the lesions induced with a lesionmaker, and stimulation directed at a particular target exerts more specific effects on particular symptoms of Parkinson’s disease (PD). Thus, whenever stimulation therapy is to be applied to patients, an effective stimulation target must be selected depending on the nature of the symptom to be improved. For example, ventral intermediate nucleus (VIM) thalamic stimulation is able to stop tremor completely, but has no appreciable effects on other symptoms. Bilateral globus pallidum interna (GPi) stimulation and subthalamic nucleus (STN) stimulation have been applied to reduce the pathological inhibitory effects on the thalamocortical circuit from the GPi and/or the substantia nigra pars reticular nucleus (SNr), which produces the final output of the basal ganglia circuits. However, there is still controversy about both the indications for and the role of GPi versus STN stimulation. This article presents a review of recent reports that describe follow-up results and double-blind studies on the signs for relief of each type of parkinsonian symptom, following GPi or STN stimulation. It also includes a discussion of how further research should be organized in order to identify whether GPi or STN stimulation exerts the greatest effect on particular kinds of parkinsonian symptoms.

The avoidance of the development of secondary brain damage following head injury is a key point in treating severe brain injury. Recently cerebral perfusionpressure (CPP)-based management, in which volume expansion and vasopressor therapies are often employed to reduce the risk of such secondary brain damage, has improved the long-term neurological outcome as compared with traditional intracranial pressure-based management. However, it is indicated that CPP-based management may possibly induce severe vasogenic edema and intracerebral bleeding, if the patients suffer from disturbances in vascular response ability including vasospasm caused by head injury. Therefore, it is important to know the condition of the vascular response ability, before applying CPP-based management. Recently, there have been many excellent papers about cerebrovascular reactivity, including vasospasm following head injury. The purpose of this review is to evaluate the most advanced diagnostic methods at the bedside as a monitor for checking the disturbance of the cerebral vascular response ability, including vasospasm following head injury, in order to get a much better outcome by CPP-based management for head injury patients.

A case of central neurocytoma was studied by electron microscopic and immunohistochemical methods. Immunohistochemical examinations showed the tumor cells to be positive for neuron-specific enolase, sporadically positive for synaptophysin, and negative for glial fibrillary acidic protein. The Ki-67 (MIB-1) positive index value for the tumor cells was a low 1.5%. Ultrastructurally, thin cytoplasmic processes of tumor cells showed differentiation to neuronal cells containing parallel bundles of microtubules and abortive synapses with dense core vesicles and/or clear vesicles. Microvessels composed of endothelial cells without fenestrations and tight junctions in the endothelial clefts appeared in fibrillary stromas as revealed by light microscopy. Neurosecretory granules in thin cell processes may have been secreted around microvessels.

One major event taking place at the moment of traumatic brain injury in neuronal cells is the occurrence of massive ionic fluxes across the plasma membrane, which can be referred to as traumatic depolarization (TD). Unlike spreading depression, TD can occur over wide brain areas simultaneously. Furthermore, recovery from TD often takes far longer than recovery from ionic perturbation elicited by the passage of a single wave of spreading depression. Neuronal cell damage caused by ischemic brain injury is also initiated by massive ionic fluxes, termed anoxic depolarization. The occurrence of similar ionic events in these two forms of brain injury may account for the genesis of diffuse ischemia-like damage without actual episodes of hypoxia or ischemia in traumatic brain injury. We review the data indicating that excitatory amino acids (EAA) may play a vital role in producing TD, and that such EAA-mediated ionic perturbation is responsible for a number of posttraumatic events including subcellular metabolic dysfunction and cellular responses such as microglial activation and astrocytic transformation. TD may represent one of the most important mechanisms of diffuse neuronal cell dysfunction and damage associated with traumatic brain injury.

In order to clarify the relationship between calcium mobilization and morphological changes in the arterial wall after subarachnoid hemorrhage, electron microscopic histochemical assessments of the intracellular calcium in the arterial wall of human subjects showing vasospasm angiographically were conducted. Intracellular calcium ions in the arterial wall after subarachnoid hemorrhage were significantly more numerous than those of the control specimens. However, reaction products of calcium ions in the arterial wall were distributed mainly in the areas which morphologically revealed spastic changes such as myonecrosis and vacuoles, and there were no or extremely few reaction products of calcium ions in the areas showing no morphological changes in the arterial wall. These findings were consistent with the data for a feline model with experimental subarachnoid hemorrhage previously studied by the authors and indicated that increased intracellular calcium mobilization detected histochemically might be related to the morphological changes in the arterial wall after subarachnoid hemorrhage.

✓ Persistent hemiballismus after stroke is often difficult to treat. The ballistic movement is sometimes so violent that progressive exhaustion results. The authors report two such cases, which were successfully treated by chronic thalamic stimulation. The lesions responsible for the ballistic movement in these patients were located near the subthalamic nucleus and in the putamen, respectively. The thalamic nucleus ventrolateralis and nucleus ventralis intermedius were stimulated with 0.2 to 0.3 msec pulses at 50 to 150 Hz and 4 to 7 V continuously during the day. Several weeks later, complete control of the hemiballismus was achieved during stimulation. The improvement was clearly not attributable to spontaneous recovery, because ballistic movement reappeared after termination of the stimulation. The stimulation has remained effective for more than 16 months in both cases without any serious complications. Chronic thalamic stimulation appears to be useful for controlling persistent hemiballismus, as it is for other involuntary movement disorders.

The authors describe a child who suffered from massive intracerebral bleeding due to rupture of a cerebral arteriovenous malformation associated with Klippel-Trenaunay syndrome (KTS). Neurovascular lesions have been regarded as uncommon in KTS; however, our case may indicate the need for neurovascular scrutiny in patients with this syndrome.

We previously reported the post-ischemic potentiation (PIP) of synaptic efficacy in hippocampal Schaffer collateral/CA1 responses of the rat beginning at 6–8 h following 12 min transient cerebral ischemia in vivo. The present study demonstrated that repetitive stimulation with a relatively low frequency (5 Hz, 6 s), which produced short-lasting afterdischarges (ADs; duration, 4.49 ± 4.26 s; n = 7) in sham-controls, resulted in prolonged ADs (duration, 26.33 ± 12.63 s; n = 6; P < 0.001) at the same perio after ischemia. The PIP was not affected by 2-amino-5-phosphonovalerate (APV) administered via microdialysis at 7 h post-ischemia. The prolonged ADs in response to repetitive stimulation were, however, reversed to short-lasting ADs (duration, 7.13 ± 1.44 s; n = 4; P < 0.02) by the same procedure, leaving the response to single stimulation unaffected. These findings suggest that, during the reperfusion period, Ca2+ influx into the CA1 pyramidal cells can be greatly increased through N-methyl-d-aspartate (NMDA) receptor-coupled ion channels if appropriately timed multiple synaptic inputs bombard these cells. Such Ca2+ influx may contribute to delayed death of CA1 pyramidal cells after transient cerebral ischemia if synaptic activity is maintained at relatively high levels during the reperfusion period.

We performed magnetic resonance angiography (MRA) in 12 children with a suspected or angiographically proven moyamoya disease. MRA was performed by the three-dimensional, time-of-flight technique and, successfully depicted the primary abnormalities in the distal carotid arteries in 10 out of of the 12 patients. In the other two patients, poor visualization of the intracranial vasculature strongly suggested the presence of the disease. On MRA, moyamoya vessels were visible in eight patients. The presence of anastomoses was also confirmed by MRA in seven of the 10 patients who had undergone encephalo-duro-arterio-synangiosis. Our findings suggest that MRA may be the tool of choice for selecting patients to undergo conventional angiography. However, establishing a definite diagnosis still requires some improvements in the delineation of the fine vasculature.

✓ Jugular bulb oxygen saturation (SjO2) was monitored during preoperative embolization procedures in a consecutive series of 15 patients with large supratentorial arteriovenous malformations (AVM's) in order to test the hypothesis that changes in the shunt flow ratio can be continuously evaluated from the SjO2. A fiberoptic catheter was placed at the dominant jugular bulb. The SjO2 measured using jugular blood withdrawn before embolization was significantly higher than the SjO2 measured at the end of the final embolization procedure (mean ± standard deviation 84.1% ± 12.7% vs. 74.2% ± 10.9%, p < 0.0001), showing a positive correlation with the AVM volume (r = 0.66, p < 0.001). Continuous monitoring of SjO2 via the fiberoptic catheter revealed a progressive decrease in association with the embolization procedures. Microsurgical resection of the AVM was performed at 1 to 2 weeks after the final embolization. Cases in which postoperative hemispheric deformation was revealed on computerized tomography demonstrated a higher SjO2 at the end of embolization compared to that in the remaining cases (81.6% ± 8.6% vs. 67.8% ± 8.4%, p < 0.008). Hemispheric deformation was observed in all cases in which the SjO2 did not decline to a level below 90% following embolization. The risk of severe hyperemic complications appeared to be greatly diminished when the SjO2 fell to below 80%. Assuming that the oxygen saturation of the perfusion flow (SjpO2) ranges from 50% to 75%, the ratio of the shunt flow to total flow at an SjO2 of 90% was estimated to be 0.6 to 0.8 based on the following equation: shunt flow/(perfusion flow + shunt flow) = (SjO2 − SjpO2)/(arterial oxygen saturation − SjpO2). These results suggest that monitoring the SjO2 provides real-time information concerning the progress of embolization and helps to determine whether the embolization has progressed sufficiently to avoid postoperative hyperemic complications.

A favorable case of recurrent medulloblastoma, in which 19 years has elapsed with combination therapy due to surgery, radiation and chemotherapy since the initial operation, is reported. The case was a male of age 12 who was admitted due to medulloblastoma of the classical type. Tumor recurrences were observed 3 times within 7 years after the initial operation and radiation treatment. At the 3rd recurrence, a large tumor was found in the cerebellar vermis and left cerebellar hemisphere on CT with CSF dissemination and a high NSE level in the CSF (62 ng/ml). Only chemotherapy by intravenous administration of 2 courses of 120-150 mg ACNU (1.7-2.2 mg/kg) and 4 mg vincristine (0.06 mg/kg) with intrathecal administration of methotrexate was given at this time. The tumor image and gait disturbance with radicular pain disappeared completely and the NSE level in the CSF improved to within the normal range (5.4 ng/ml). The patient continues in complete remission, with a Karnovsky performance status of 100% at 4 years after the 3rd recurrence. We report full details of this case in which active treatments consisting mainly of chemotherapy proved to be effective for recurrent medulloblastoma, even though its prognosis is generally very unfavorable.

A patient with hypertensive intracerebellar haemorrhage, who recovered from impending tonsillar herniation with emergency haematoma evacuation, showed persistent absence of auditory brainstem responses. The patient demonstrated a preserved stapedius reflex and hearing after recovery, indicating that the auditory brainstem pathway was not completely disrupted. We suggest that the loss of the auditory brainstem response (ABR) could be accounted for by impulse asynchrony along the auditory brainstem pathway. The existence of such a case implies that persistent absence of the ABR is not always indicative of irreversible brainstem damage and a poor outcome following severe brain injury.

✓ In order to determine adequate therapeutic approaches for cavernous malformations of the third ventricle, the authors reviewed a series of five such malformations managed at their institution and nine others reported in the literature. Four subgroups were identified in terms of the site of origin and could be characterized by different clinical manifestations: visual field defects and endocrine function deficits in patients with malformations in the suprachiasmatic region (six cases); symptoms caused by hydrocephalus in those with malformations in the foramen of Monro region (five cases); and deficits of short-term memory in those with malformations in the lateral wall (two cases) or of the floor of the third ventricle (one case). Unlike cavernous malformations at other locations, malformations of the third ventricle frequently demonstrated rapid growth (43%) and mass effects (71%). The surgical or autopsy findings suggested that the growth was attributable to repeated intralesional hemorrhages. Extralesional hemorrhage was also not uncommon, occurring in 29% of patients. Such tendencies require the adoption of a more aggressive approach to this particular group of cavernous malformations as compared to those in other locations. The risks of regrowth and extralesional hemorrhage appear to be reduced only by complete excision. The surgical approaches adopted should be aimed at providing the best access to the site where the malformation has arisen. The translamina terminalis approach for cavernous malformations in the suprachiasmatic region, the transventricular or transcallosal interfornicial approaches for those in the foramen of Monro region and the transvelum interpositum approach for those in the lateral wall or the floor of the third ventricle appear to be appropriate. In order to select the adequate surgical approach, precise diagnosis of the site of origin is crucial. In addition to neuroimaging techniques, the patient's initial symptoms provide valuable information.

In order to determine the role of excitatory amino acids (EAAs) in free fatty acid (FFA) liberation during cerebral ischemia, we examined the effect of in situ administration of kynurenic acid, a broad-spectrum antagonist of EAA receptors, by microdialysis on the increase in FFA levels during ischemia in the rat hippocampus. A transient rapid increase in FFA levels, superimposed on a continued slow increase, was observed beginning at 1-2 min after ischemia induction. The early rapid increase in FFAs was profoundly inhibited by kynurenic acid, suggesting that EAAs are critically involved in the early phase of FFA liberation. Development of massive ionic shifts during cerebral ischemia can be delayed for several minutes by kynurenic acid administered by the same procedure, suggesting a vital role for EAAs in the early appearance of anoxic depolarization. The observed inhibition of early FFA liberation may thus be attributable to the delay in development of massive ionic shifts and resultant neurotransmitter release which may activate phospholipase A2 and C.

Calcium channel blockers such as diltiazem are being explored as agents to reduce or prevent cerebral vasospasm following subarachnoid hemorrhage (SAH). Yet little is known concerning changes over time in the calcium ions in the arterial wall after subarachnoid hemorrhage even when calcium channel blockers are used. The results imply that the massive increase of calcium ions in the smooth muscle cells in the early stages of SAH may be related to morphological changes in the spastic vessels in the subacute stage of SAH and calcium ion blockers might be useful in reducing organic changes in the vessels by the inhibition of calcium overloading.

The present study examined the functional changes in the hippocampal CA1 pyramidal cell system in vivo occurring after 12-min forebrain ischemia in the rat. A population excitatory postsynaptic potential and orthodromic population spike of CA1 pyramidal cells to stimulation of the Schaffer collaterals were potentiated at 6-8 h post-ischemia. These changes were not associated with an increase in excitability of the CA1 pyramidal cells as evaluated from the antidromic population spike induced by alveus stimulation, suggesting the presence of an increased synaptic efficacy. The post-ischemic potentiation was prevented by pretreatment with the N-methyl D-aspartate (NMDA) receptor antagonist, MK801, in a dose-dependent manner. These findings suggest that 12-min forebrain ischemia in the rat activates NMDA receptors, which results in an increase in synaptic efficacy to the CA1 pyramidal cells at 6-8 h post-ischemia.

✓ Analysis of the authors' experience over the last 10 years has indicated that excellent pain control has rarely been obtained by thalamic relay nucleus stimulation in patients with thalamic pain. In the present study, 11 patients with thalamic pain were treated by chronic stimulation of the precentral gyrus. In eight patients (73%), the stimulation system was internalized since excellent pain control was achieved during a 1-week test period of precentral gyrus stimulation. In contrast, no clear effect was noted or the original pain was even exacerbated by postcentral gyrus stimulation. The effect of precentral stimulation was unchanged in five patients (45%) for follow-up periods of more than 2 years. In the remaining three patients, the effect decreased gradually over several months. This outcome was significantly better than that obtained in an earlier series tested by the authors with thalamic relay nucleus stimulation (p < 0.05). The pain inhibition usually occurred at intensities below the threshold for production of muscle contraction (pulse duration 0.1 to 0.5 msec, intensity 3 to 8 V). When good pain inhibition was achieved, the patients reported a slight tingling or mild vibration sensation during stimulation projected in the same area of distribution as their pain. The authors discuss the possibility that, in deafferentation pain, sensory neurons below the level of deafferentation cannot exert their normal inhibitory influences toward deafferented nociceptive neurons because of the development of aberrant connections. Thus, while stimulation of the first- to third-order sensory neurons at the level of the thalamic relay nucleus or below cannot bring about good pain inhibition in patients with thalamic pain, activation of hypothetical fourth-order sensory neurons through precentral stimulation may be able to inhibit deafferented nociceptive neurons within the cortex. None of the patients developed either observable or electroencephalographic seizure activity.

The effects of indeloxazine on the ischemia-induced death of hippocampal CA1 pyramidal cells following transient cerebral ischemia were examined in the mongolian gerbil. Increased survival of CA1 pyramidal cells was demonstrated in animals pre- and post-treated with indeloxazine. Increased survival of CA1 pyramidal cells was, however, not demonstrated in animals post-treated but not pre-treated with indeloxazine. A previous study has demonstrated that indeloxazine increases the glucose and adenosine triphosphate (ATP) contents in the brain probably through an enhanced capability of oxidative phosphorylation. It has been reported that increases in the glucose and ATP contents in the brain before ischemia delay the onset of massive ionic fluxes during ischemia. The delay in onset of this ionic event may help to protect these cells from death. The present data suggest that energy state before ischemia may play an important role in the protective effect of indeloxazine.

A rare pituitary adenoma associated with Rathke's cleft cyst was discovered incidentally in a 44-year-old male admitted after head trauma. Neurological and physiological examination found no abnormalities, except for panhypopituitarism. Computed tomography and magnetic resonance imaging demonstrated a solid mass in the sellar cavity with suprasellar extension, associated with a cystic mass extending into the third ventricle. The tumor was removed subtotally by the transcranial approach. Light microscopy demonstrated that the cyst wall was composed of ciliated columnar cells, cuboidal cells, and goblet cells, and the solid part indicated chromophobe pituitary adenoma. Immunohistochemistry demonstrated that a few adenoma cells were positive for prolactin and the cyst wall cells were positive for cytokeratin and negative for S-100 protein.

One hundred and seven patients in vegetative state (VS) were evaluated neurologically and electrophysiologically over 3 months (90 days) after the onset of brain injury. Among these patients, 21 were treated with deep brain stimulation (DBS). The stimulation sites were the mesencephalic reticular formation (two patients) and centromedian-parafascicularis nucleus complex (19 cases). Eight of the patients recovered from VS and were able to obey verbal commands at 13 and 10 months in the case of head trauma and at 19, 14, 13, 12, 12 and 8 months in the case of vascular disease after comatose brain injury, and no patients without DBS recovered from VS spontaneously within 24 months after brain injury. The eight patients who recovered from VS showed desynchronization on continuous EEG frequency analysis. The Vth wave of the auditory brainstem response and N20 of the somatosensory evoked potential could be recorded, although with a prolonged latency, and the pain-related P250 was recorded with an amplitude of7 μV. Sixteen (14.9%) of the 107 VS patients satisfied these criteria in our electrophysiological evaluation, 10 of whom were treated with DBS and six of whom were not treated with DBS. In these 16 patients, the recovery rate from VS was different between the DBS therapy group and the no DBS therapy group (P0.01, Fisher's exact probability test) These findings indicate that DBS may be useful for the recovery of patients from VS if the candidates are selected on the basis of electrophysiological criteria.

Our previous studies have shown that kynurenic acid (KYN), a broad-spectrum antagonist of excitatory amino acids (EAAs), administered in situ through a dialysis probe can delay the massive ionic fluxes in the rat hippocampus during cerebral ischemia. The present experiments demonstrated that the same procedure attenuates the increase in extracellular concentration of lactate ([lactate]e) during ischemia as measured by microdialysis. This finding suggests that the lactate accumulation is partially caused by a sudden increase in energy demand due to the rapid ionic fluxes through EAA-coupled ion channels. This inference is consistent with the hypothesis that the earlier ionic event during ischemia is a cause of energy depletion, rather than the result merely of energy failure. The present experiments also revealed that KYN administered by the same procedure attenuates death of hippocampal CA1 pyramidal cells after 5-min transient ischemia in gerbils. Since lactate accumulation is likely to be an important factor affecting cell viability, the protective effect of KYN may be attributable, in part, to inhibition of lactate accumulation.

Primary cranial Ewing's sarcoma is exceptionally rare. Only ten cases of such a tumor had been reported heretofore in the literature. We describe a case of primary Ewing's sarcoma occurring in the temporal bone. The tumor was surgically excised, and the patient underwent radiation and chemotherapy. Neither recurrence nor distant metastasis was noted at 12 months after surgery. Although the prognosis of Ewing's sarcoma in general is often poor because of early metastasis to the lungs and/or to other bones, a review of the literature suggested that the same tumor occurring in the cranium can often be successfully managed by intensive therapy with radical excision and radiochemotherapy. This inference was supported by the case reported here.

Ultrastructural examinations of the cerebral vascular wall following subarachnoid hemorrhage (SAH) demonstrated that collagen fibrils developed in the muscle layer near the adventitia in the early stage of SAH and increased in number and volume with time. These findings suggest that accelerating factors of collagen synthesis in the muscle layer may be released from the adventitial side, and collagen synthesis is induced by extravascular factors. The changes of collagen volume with time suggest collagen to be an important phenomenon of persistent vasospasm after SAH. Histoimmunological studies showed that increased collagen fibers in the tunica media were mainly type III collagen, implying that cerebral vasospasm may be related to chemical inflammation.

This study characterizes the physiological features and limitations of K+-free dialysis to detect changes in extracellular concentration of K+ ([K+]e) in the rat hippocampus in vivo. It also demonstrates the effects of Ca2+-free perfusate containing Co2+ or Mg2+, which blocks Ca2+ entry into the presynaptic nerve terminal, on the abrupt increase in [K+]e detected by this technique during cerebral ischemia. K+-free dialysis for 40 min caused no significant changes in the baseline [K+]e. In contrast, Ca2+-free dialysis for 40 min significantly reduced the extracellular Ca2+ concentration. Under this condition, together with addition of Co2+ or Mg2+ to the perfusate, the increase in [K+]e was delayed, and a delay in reaching the maximum level was observed in a dose-dependent manner. These results are consistent with the hypothesis that the initial increase in [K+]e during cerebral ischemia is related to the Ca2+-dependent exocytotic release of neurotransmitters from depolarized nerve terminals.

Previous studies have demonstrated that microdialysis is capable of detecting an abrupt and massive increase in extracellular K+ concentration ([K+]e) and a concomitant increase in extracellular concentration of excitatory amino acids (EAAs) during cerebral ischemia in the rat hippocampus in vivo. Following in situ administration of kynurenic acid (KYN), a broad-spectrum antagonist of EAAs, through the dialysis probe (5–10 mM), a delay in reaching the maximum level of increased [K+]e was observed in a dose-dependent manner. The initial component of the rapid increase in [K+]e appears to be mediated by EAAs released from nerve terminals.

Cell suspensions obtained from the fetal hippocampus were transplanted into the adult rat hippocampus at 1 or 4 weeks after transient forebrain ischemia. Only when the ischemia induced death of most of the CA1 pyramidal cells of the host hippocampus and transplantation was performed at 1 week after the ischemia, did a large number of transplanted cells survive and the most extensive dendritic growth was demonstrated by microtubule-associated protein 2 immunohistochemistry. The dendrites of the cells located in the ventral part were oriented ventrally, lining up similarly to the parallel arrangements of apical dendrites of normal CA1 pyramidal cells. These findings suggest that certain forms of trophic factors, which appear to occur in association with the presence of free terminals of afferent fibers during the earlier period after ischemic insult, are involved in the survival of and dendritic growth from transplanted hippocampal cells.

The changes in extracellular glutamate ([Glu]e) and potassium ([K+]e) in the rat hippocampus during cerebral ischemia were determined simultaneously by microdialysis in vivo. Biphasic increases in [Glu]e, i.e. an earlier rapid increase concomitant with an abrupt increase in [K+]e followed by a later slow increase, were observed. Dialysis with Ca(2+)-free perfusate containing Co2+ blocked the earlier rapid increase completely but the later slow increase only partially. These findings suggest that Ca(2+)-dependent exocytotic release from the presynaptic nerve terminals is involved predominantly in the earlier rapid increase in [Glu]d. The later slow increase in [Glu]d may be due in part to a breakdown of membrane function resulting from several causes, including a loss of the electrogenic component of the glutamate gradients across the plasma membrane, and a loss of function of the glutamate uptake system.

Intramedullary spina AVMs fed by the anterior spinal artery cannot be embolized without risking unacceptable motor deficits, since the feeding arteries may supply the corticospinal tract (CST). An 8-year-old boy underwent successful embolization of such an AVM under general anesthesia using intermittent infusion of embolic material with monitoring of the CST integrity with the corticospinal motor evoked potential (MEP). This case illustrates the value of corticospinal MEP monitoring during therapeutic procedures under general anesthesia which risk interrupting the blood supply to the CST.

✓ A case of epithelial cyst in the fourth ventricle of a 4-year-old child is described. A single epithelial layer with a clear basement membrane lining the cyst wall was observed. There were no prominent histological findings to suggest a pathogenesis for this cyst based on immunohistochemical or ultrastructural studies; however, the cyst fluid contained significant amounts of carcinoembryonic antigen. It is considered that the epithelial layer lining the cyst wall was possibly of endodermal origin.

The clinical effects and problems of intra-arterial water-soluble antitumor nitrosourea (ACNU) therapy following osmotic blood-brain barrier modification are discussed. Twenty-one patients with malignant brain tumors were divided into two groups. Group 1 consisted of 16 patients treated by operation, irradiation, and two or more courses of intracarotid infusion of ACNU 100 mg/body (1.7-2.2 mg/kg) following 20% mannitol 200 ml (1.3-1.6 ml/sec) (7 grade 4 astrocytomas, 5 grade 3 astrocytomas, and 4 others). Group 2 consisted of five patients treated by operation, irradiation, and repeated intracarotid infusion of ACNU 100 mg/body alone (grade 4 astrocytoma). The 2-year survival rate in Group 1 was 79% (11 of 14 cases followed up for longer than 2 years) and the 3-year survival rate was 67%. Five of seven grade 4 astrocytoma patients (71%) in Group 1 survived for more than 1 year 6 months, whereas four of five grade 4 astrocytoma in Group 2 died within 1 year 6 months. The measurement of the ACNU concentration in tumor tissues and blood in 11 brain tumors, after intracarotid infusion of ACNU with blood-brain barrier disruption, showed peak values in the tumor tissues of 3.02-32.53 micrograms/gm (mean, 9.67 micrograms/gm), about three to five times as high as that in blood in most cases. This method used in Group 1 appears to be relatively safe without permanent neurological deficits and offers a potential therapeutic effect when used in combination with appropriate premedication in suitable patients.

Eight cases of a persistent vegetative state caused by brain damage were treated by chronic deep-brain stimulation (stimulation target: the mesencephalic reticular formation and/or non-specific thalamic nucleus) over a period of more than 6 months. Three of the patients are currently able to communicate and to express their demands by voice and one other patient has recovered very close to this state. These four cases showed changeable spectrograms with desynchronization on continuous EEG recording and all components of the BSR and SER could be recorded except for prolonged latency of both N20 (SER) and the V wave (BSR) 2 months after the initial coma. Following chronic deep-brain stimulation, EEG and behavioural arousal responses were observed with increased r-CBF, r-CMRO2 and r-CMRGL in the whole brain tissue. After 3-6 months of chronic deep brain stimulation, the prolonged coma scale rose in four of the eight cases and three cases emerged from the persistent vegetative state. Transmitter substances and their metabolites were also found to be increased in the CSF after chronic deep-brain stimulation. Based on these findings, chronic deep-brain stimulation represents a useful kind of treatment that can lead to emergence from a persistent vegetative state, if the candidate is selected by electrophysiological studies 2 months after the initial insult and if the stimulation is applied for more than 6-8 months using a high-safety chronic deep-brain stimulating instrument.

During cerebral ischaemia, the extracellular concentration of K+ ([K+]e) increases abruptly to 50-60 mM following an initial slow increase to 6-10 mM. We have recently shown that the increase in [K+]e is significantly delayed by in situ administration of kynurenic acid, a broad spectrum antagonist of excitatory amino acids, suggesting that the catastrophic ionic fluxes occurring during ischaemia are initially mediated by EAA-coupled ion channels. In order to confirm further the role of EAAs, the changes in extracellular K+ ([K+]e) and glutamate ([Glu]e) during cerebral ischaemia were determined in the rat hippocampus by microdialysis in vivo, and the effect of dihydrokainate (DHKA), an inhibitor of the high-affinity uptake system of EAAs, was examined by in situ administration through the dialysis probe. DHKA induced a significant increase in baseline [Glu]e and facilitated the abrupt increase in [K+]e during cerebral ischaemia. These findings support the hypothesis that EAAs play a vital role in producing the rapid ionic shifts earlier during cerebral ischaemia.