Neurons with spontaneous high-frequency discharges in the central nervous system and chronic pain.

Neurons with high-frequency discharge (hyperactive neuron) were recorded in the thalamus of chronic pain patients. We created a chronic pain rat model, and recorded the discharge of high-frequency neurons by using a microelectrode in the thalamic area. The character of these high-frequency discharge neurons was assessed. Deep brain stimulation (DBS) was done in 9 patients, and motor cortical stimulation (MCS) in 2. Prior to implantation of the stimulation electrodes, extracellular unitary activity was recorded and local microstimulation was done by the same microelectrode. From the ventrocaudal (Vc) nucleus of the chronic pain patients, hyperactive neurons were recorded. There were three types of discharge patterns in interval histograms. Some hyperactive neurons showed firing suppression for a short time period by intravenous administration of phenytoin and calcium antagonist (Nicardipine). In animal experiments, unilateral dorsal root sectioning from C5 to Th1 were made in male Wistar rats according to the method of Lombard et al. (1979). A few months after the operation, hyperactive neurons were recorded from the thalamic nuclei and lemniscus medialis. The firing patterns and distribution of hyperactive neurons were very similar to those of humans. Sensorimotor cortical electrical stimulation showed a reduction of firing in the hyperactive neurons. Iontophoretical application of glutamate yielded an increase in firing. In contrast, GABA and NMDA antagonist MK-801 revealed remarkable firing suppression. These results suggest that hyperactive neurons may correlate with the glutamatergic, especially NMDA and GABAergic receptor or fibers.

Lesioning of the inferior olive using a ventral surgical approach. Characterization of temporal and spatial astrocytic responses at the lesion site and in cerebellum.

Activated astrocytes, intrinsic components of both local and remote (axonal target regions) central nervous system injury responses, are now recognized as active metabolic and regulatory mediators in many neurological disorders. To further define these responses, we devised a new ventral surgical approach to unilaterally lesion the inferior olivary nuclear complex, which has a single predominant remote target, the cerebellum. Activated astrocyte number, volume, and density, as well as the total volume of brainstem involved in the astrocytic response, all peaked at postlesion day (pld) 4, returning toward, but not to, unoperated control values at pld 24 (p < 0.05). In contrast, the peak astrocyte response in the cerebellum was delayed, being greatest at pld 6 (p < 0.05 compared to control or pld 2). These responses were associated with increases in overexpression of S100 beta, an astrocyte-derived neurite growth factor, and with an increase in cerebellar steady-state levels of a neuronal injury response protein, the beta-amyloid precursor protein (beta-APP). This is similar to correlated increases in these two proteins that are found in epilepsy and Alzheimer disease. Our studies defining remote astrocytic and neuronal responses may be important for understanding glial-neuronal mechanisms underlying the spread of neuropathological changes in conditions such as Alzheimer disease.

An extensive cranial base meningioma extending bilaterally into Meckel's cave: case report.

OBJECTIVE AND IMPORTANCE: A patient with an extensive cranial base meningioma that included bilateral invasion of Meckel's cave underwent surgical resection and had an unexpected rare complication, malocclusion from bilateral trigeminal dysfunction. CLINICAL PRESENTATION: A 19-year-old male patient was admitted to our hospital with alternating painful ophthalmoplegia. He had been blind since the age of 10 years. At the time of admission, neurological findings included bilateral visual loss and optic atrophy. Magnetic resonance images showed an extensive tumor located at the planum sphenoidale, tuberculum sellae, and bilaterally at Meckel's cave and the medial tentorial incisura. INTERVENTION: The patient underwent a two-stage operation. During the first procedure, the masses in the planum sphenoidale, tuberculum sellae, and the left side of Meckel's cave were excised intradurally. At the second operation, the mass in the right side of Meckel's cave was excised extradurally and the tentorial mass was removed intradurally. The patient's postoperative course was complicated by bilateral trigeminal nerve dysfunction, which caused malocclusion. CONCLUSION: Bilateral dysfunction of the trigeminal nerve may cause a number of problems. Thus, extreme caution must be taken to preserve the function of this nerve.

[Histopathological examinations of dural arteriovenous malformations of posterior fossa].

Two cases of dural arteriovenous malformation (DAVM) of the posterior fossa were presented and a histopathological examination was described. After embolization of the feeding arteries, DAVMs of the posterior fossa were removed with the adjacent sinus. Serial sections of the surgical specimens showed an abnormal mass with dilated, tortuous vessels of varying diameters in the sinus wall, and partially hyalinized connective tissue around the vessels. The elastic lamina of the sinus wall was interrupted and a mass of abnormal vessels developed into the subintimal layer of the sinus. Fistulas, about 200 microns in diameter, were formed between arterialized dural veins and dural arteries which had obvious internal elastic lamina. An opening of the fistula of the abnormal vessel, 25 microns in diameter, to the sinus lumen was also seen. No stage of organized thrombus could be seen in the sinus lumen. These findings strongly suggested that physiologically existing arteriovenous fistulas within the dura mater, which have been reported by Kerber et al, had developed due to many factors which increase intracranial pressure. They protruded into the sinus lumen in such a way that it could cause stenosis or obstruction of the sinus. In conclusion it can be said that an obstructive lesion of dural sinus is considered of itself to be DAVM in most cases and sinus thrombosis is the result of the DAVM.

[Transarterial platinum coil embolization for direct carotid-cavernous fistula].

Two cases of direct carotid-cavernous fistula (CCF) were treated by transarterial platinum coil embolization (TACE) following unsuccessful transarterial balloon embolization (TABE). Case 1 was a 47-year-old man who complained of pulsatile left exophthalmos, chemosis and bruit. Left carotid angiograms showed a CCF with anterior, posterior and cortical venous drainage. Near total obliteration of the CCF was achieved by TABE, but it showed recurrence in the next morning. At this time, left carotid angiograms showed a CCF which drained only into the cortical veins via the enlarged sphenoparietal sinus. Because of high risk of intracranial hemorrhage, TACE was performed immediately. The result was successful. Case 2 was an 82-year-old woman who suffered from traumatic subarachnoid hemorrhage. First right carotid angiograms showed a small CCF which drained only into the inferior petrosal sinus. Right exophthalmos, swelling of the eyelids, severe eye pain and bruit appeared gradually. The second right CAG performed three months after the head trauma showed markedly dilated superior ophthalmic vein which was the new main draining root of the CCF. Because of progressive symptoms, TACE was performed immediately after the angiography, which proved successful. Direct CCFs must be treated aggressively because they don't cure by spontaneous obstruction of fistula. Although TABE is the first choice for direct CCF, complete occlusion of CCF in difficult in some cases. Those cases have; 1) small fistula of CCF for balloon insertion, 2) large fistula for occlusion by balloons, 3) not enough space for inserting a balloon after recurrence of CCF, and 4) sharp objects (bone fracture fragments, foreign objects) may puncture the balloon. If TABE couldn't provide successful treatments, TACE should be considered as an alternative treatment for direct CCF after angiography without delay because it is less complex compared with TABE.

Characteristics of neurons with high-frequency discharge in the central nervous system and their relationship to chronic pain. Experimental and clinical investigations.

High-frequency extracellular unitary activity was recorded mainly in the ventral caudal nucleus of the thalamus in chronic-pain patients. These high-frequency discharge (hyperactive) neurons shows three types of discharge pattern with different interval histograms. Some of these hyperactive neurons were suppressed by the administration of a calcium antagonist (nicardipine). In an experimental study, chronic-pain models were made in rats according to the method of Lombard et al. (1979). From these animals, hyperactive neurons were recorded from the contralateral thalamic nuclei, lemniscus medialis. Hyperactive neurons were examined via electrical stimulation of and/or iontophoretic application. The results suggest that there is some relationship to the glutamatergic and GABAergic (probably GABAA) fibers or receptors.

Midlatency auditory evoked potentials and the startle response in the rat.

The P13 midlatency auditory evoked potential in the rat is (i) sleep state dependent, (ii) undergoes rapid habituation and (iii) is blocked by the cholinergic antagonist scopolamine. As such, the P13 potential in the rat shows the same characteristics as the P1 (or P50) potential in the human. These potentials are thought to be mediated, at least in part, by the cholinergic arm of the reticular activating system. Previous studies have linked the reticular activating system with the startle response. The present study was undertaken to explore this relationship by simultaneously recording the P13 potential and the electromyographically recorded startle response using stimuli designed to elicit each response. Simultaneous recordings from the vertex and neck musculature following auditory click stimuli showed that: (i) the mean threshold of the P13 potential was 69.3 +/- 1.9 dB, while that for the startle response was 87.9 +/- 6.4 dB; (ii) the P13 potential was present during waking and paradoxical sleep, but absent during slow-wave sleep, while the startle response was present reliably only during waking; (iii) both responses habituated in response to paired stimuli, but the startle response was more habituated than the P13 potential; and (iv) both responses were facilitated by trains of stimuli in a similar manner. Recordings carried out from the auditory cortex verified that the primary cortical response had properties different from the P13 potential; i.e. it was present during all sleep-wake states, had a lower threshold and did not habituate rapidly. Finally, different patterns of startle responses were detected in the neck muscles. In every case, the P13 potential occurred during the middle, inhibitory phase of the startle response. These results suggest that the P13 potential and the startle response share response features, but the P13 potential appears to be more sensitive to auditory stimulation and to sleep-wake states. The startle response may be modulating descending systems by priming the spinal cord to respond in a "fight vs flight" fashion. On the other hand, the P13 response may be modulating ascending systems by triggering thalamocortical activity and resetting descending systems to allow novel motor strategies.

[Management of hydrocephalus in the case with pineal region tumor].

When patients have a pineal region tumor, they frequently present with hydrocephalus. However, not all of patients with pineal region tumor continue to suffer from hydrocephalus after tumor therapy. We have retrospectively studied 24 patients, and found that 20 patients (83.3%) have hydrocephalus, and 5 patients (20.8% of all cases and 25.0% of hydrocephalic cases) still have a shunt. We confirmed how fast germinoma diminished under radiation therapy. Irradiation dosage ranged between 30 and 65.8 Gy. Using 10 Gy, germinoma volume decreased to 20.2% of pre-irradiation size. Furthermore, 6 patients who did not receive surgical management for hydrocephalus before radiotherapy did not require a shunt subsequently. Therefore, we concluded that most of pineal germinoma cases do not need surgical management for hydrocephalus, except in those cases where there is pineal apoplexy and aqueductal dissemination.

Regulation of L-DOPA production by genetically modified primary fibroblasts transfected with retrovirus vector system.

Although intracerebral grafting has become established as a new strategy for the treatment of Parkinson's disease, there are many problems regarding such grafts. We focused on the grafting of primary skin fibroblasts. Rat primary skin fibroblasts were transfected with a retrovirus vector containing cDNA of human tyrosine hydroxylase (TH) type 1 (LTHSNL) or of cytomegalovirus promoter (CTHSNL) as a foreign promoter. In these genetically modified fibroblasts, L-DOPA production and release were analyzed in vitro by immunocytochemistry and high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Being supplemented with the biopterin (BH4:(6R)-L-erythro-tetrahydrobiopterin) cofactors required for TH activity, these cells produced and released L-DOPA into the culture medium. When CTHSNL and BH4 were combined, L-DOPA production increased with time, regardless of the number of cell passages, or the duration of liquid nitrogen freezing. This suggests that the foreign gene (THcDNA) containing retrovirus vector integrates into the chromosomal DNA of the target cells (fibroblasts). Primary fibroblasts can be easily obtained and cultured. Thus, genetically modified primary skin fibroblasts transfected with a retrovirus vector system containing the TH cDNA may be promising grafts for transplantation and gene therapy in Parkinson's disease.

[Cranio-orbital zygomatic extradural approach for cavernous sinus or Meckel's cave tumors].

Direct surgery to cavernous sinus (CS) lesions has become one of the optimal treatments based on advancement in microsurgical anatomy and imaging modality, and the progress of microsurgical techniques. We have removed the CS or Meckel's cave tumors extradurally when they do not extend intradurally, using modified Al-Mefty's cranio-orbital zygomatic craniotomy. Three CS tumors; trigeminal neurofibroma, squamous cell carcinoma and chondrosarcoma, and a Meckel's cave meningioma were reported. Total removal was achieved in all but one (case 4). Postoperative complications were permanent ophthalmoplegia in one, transient ophthalmoplegia in one, subcutaneous CSF accumulation in two and trigeminal dysfunction in one. The extradural approach can be the first choice of methods for total removal of tumors when they are confined to the CS or Meckel's cave.

Modified petrosal approach using cosmetic osteoplastic craniotomy with NEURO-SAT guidance.

The petrosal approach has become a routine procedure for petroclival lesions, but there are some disadvantages such as the time-consuming craniotomy during surgery and depressed deformity of the mastoid area after surgery. To solve these disadvantages, we modified the petrosal approach. Before surgery, the three-dimensional points of the sigmoid sinus and semicircular canals are calculated on computed tomography scan and are input to a computer. A single temporooccipital bone flap is made, and the outer table of bone overlying the mastoid is preserved by forming a narrow groove with a small air drill and cutting the outer table with a chisel. After removing these two free bone flaps, mastoidectomy is performed guided by NEURO-SAT (neuronavigation by computer-assisted frameless stereotaxy). The mastoid bone can be drilled out safely and quickly. The two bone flaps are connected and replaced at the end of the procedure. Osteoplastic petrosal craniotomy guided by NEURO-SAT can achieve a quick craniotomy and satisfactory cosmetic result.

[A successfully operated case of tuberous sclerosis presenting with intractable epilepsy].

A 20-year-old male patient with tuberous sclerosis was admitted to our hospital complaining of intractable epilepsy. He had been suffering from frequent seizures despite anticonvulsant treatment since the age of 1 year. CT scan and magnetic resonance images showed multiple calcified lesions at the paraventricle and temporal lobe on both sides. Electroencephalogram showed left temporal lobe dominant spike waves. After deep electrodes were inserted into the left amygdala and hippocampus and subdural electrodes were placed on the left temporal cortex, clinical seizures were monitored by video and EEG. The primary focus was found in the amygdala. Left temporal lobectomy was carried out through the cranio-orbital zygomatic approach. Postoperatively, the patient has been seizure-free for one year. Despite multiple intracerebral lesions in tuberous sclerosis, resection of the primary epileptogenic focus is needed to solve the seizure problem if the focus is localized.

[Histopathological analysis of herniated cerebellar tonsils resected from the patients with Chiari type I malformation with syringomyelia].

Cerebellar tonsillectomy is a controversial treatment for Chiari type I malformation combined with syringomyelia. To demonstrate the validity of this procedure, we evaluated the postoperative clinical course, the histopathological finding in the resected cerebellar tonsils and the MR images of four patients. The patients were all women, ranging in age from 27 to 58 years old (mean: 43 years). The postoperative follows-up period lasted from 28 to 51 months (average: 38 mos), and the neurological symptoms and signs improved in all patients. Histopathological examination of the resected tonsils revealed a loss of Purkinje cells and granule cells. Vacuolated degeneration and chromatolysis were also seen, and modified Bielschowsky stain revealed axonal degeneration. These findings appeared to be irreversible. Postoperative T1-weighted MR images of the cervical and thoracic spine demonstrated a decrease in the size of the syrinx and the disappearance of evidence of tonsillar herniation in all patients. Postoperative phase-contrast MR images showed good CSF pulsation in the subarachnoid space at the craniocervical junction in all three patients examined. It was possible to avoid surgical complications by using careful microsurgical techniques. Based on these results, we concluded that cerebellar tonsillectomy is an adequate surgical strategies for treating Chiari type I malformation associated with syringomyelia.

[L-DOPA-producing primary fibroblasts genetically modified with a retrovirus vector system].

Although intracerebral grafting has become a new strategy for the treatment of Parkinson's disease, many problems related to the grafts remain. We focused on primary skin fibroblasts as grafts. Rat primary skin fibroblasts were transfected with a retrovirus vector containing the cDNA of human tyrosine hydroxylase (TH) (pLTHSNL) or cytomegalovirus promoter (pCTHSNL) as a foreign promoter, and catecholamine production and release by these genetically modified fibroblasts, were analyzed in vitro immunocytochemically and by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The cells were supplemented with biopterin (BH4; (6R)-L-erythro-tetrahydrobiopterin), a cofactor required for TH activity, and they produced and released L-DOPA into the culture medium. When exposed to the combination of a foreign promoter and BH4, L-DOPA production increased in a time-dependent manner, and was unaffected by the number of cell-passages or the duration of liquid-nitrogen freezing. This suggests that the foreign gene (THcDNA)-containing retrovirus vector had integrated into the chromosomal DNA of the target cells (fibroblasts). Primary fibroblasts can be easily obtained and cultured. Thus, genetically modified primary skin fibroblasts transfected with THcDNA using this retrovirus vector system appear to be a promising graft for transplantation and gene therapy of Parkinson's disease in the future.

Transient P300 abnormality of event-related potentials following unilateral temporal lobectomy.

Event-related potentials (ERP) were recorded during auditory oddball tasks for a patient prior to and soon after left anterior temporal lobectomy. The N100 amplitude decreased bilaterally although the latency did not change after the lobectomy. The P300 amplitude decreased in the left hemisphere at 1 and 2 weeks after surgery, then recovered to the pre-operative level at 4 weeks. These findings suggest that the medial temporal structure participates in the generating system of P300.

Astrocytoma linked to familial ataxia-telangiectasia.

A 7-year and 11 month-old girl with cerebellar astrocytoma linked to familial ataxia-telangiectasia (AT) is presented. She was born as the 7th girl of a woman with aortic arch syndrome. Two elder sisters of the patient have ataxia telangiectasia. She had immunodeficiency, and cerebellar ataxia, but had no oculocutaneous telangiectasia. The risk of cancer developing in AT patients is about 1,200 times greater than that in age-matched controls. With regard to central nervous system tumours, seven primary tumours have been reported, such as 3 cases of medulloblastoma and 4 cases of glioma. Members of AT families who were under the age of 45 had a risk of dying of a malignant neoplasm five times greater than in the general population. However, there were no reports of glioma in AT families. In this case, it is suggested that IgA deficiency linked to familial AT may have contributed to the development of astrocytoma.

Symptomatic intraventricular arachnoid cyst in an elderly man.

A case of intraventricular arachnoid cyst in an elderly man is reported. A 63-year-old man developed a progressive gait disturbance over a five-year period. CT scan showed a large cyst in the left lateral ventricle which was negative to contrast enhancement. CT cisternography revealed gradual accumulation and more than 48 hours retention of contrast medium in the cyst. The patient underwent left frontal craniotomy, and the cyst wall was partially resected for histopathological examination. Although limit microscopic examination could not establish a diagnosis, arachnoid cyst was diagnosed by electron microscopic findings. Biochemical analysis did not detect any difference between cyst fluid and CSF obtained during surgery. It is suggested that a ball-valve mechanism caused progressive enlargement of the cyst and gradual development of symptoms in this elderly patient.

[Sequential change of cerebral angiography in a case of cerebral angiitis following herpes zoster ophthalmicus].

Delayed neurological symptoms and signs following herpes zoster ophthalmicus (HZO) such as "Delayed contralateral hemiplegia with HZO" are supposed to be due to ipsilateral intracranial angiitis and ischemic disorder. We experienced a rare case with ipsilateral cerebral hemorrhage following HZO. Under the diagnosis of cerebral angiitis associated with HZO, we treated her conservatively and observed sequential change of angiography for four months. A 54-year-old female, who had been treated for systemic lupus erythematosus (SLE), developed HZO on left ophthalmic nerve area. Seven weeks after the onset of HZO, she complained of headache, mild right hemiparesis, and disturbance of consciousness. Computed tomography revealed subcortical hemorrhage at the left temporo-occipital lobe. Cerebral angiography showed vascular irregularities such as segmental narrowing and sausage-like dilation on proximal portion of the ipsilateral anterior, middle and posterior cerebral arteries. Same findings were seen on peripheral portions of the posterior cerebral artery on the same side. Moreover sequential angiograms showed appearance of an aneurysm in the left middle cerebral artery (M2 potion). Under the diagnosis of cerebral angiitis associated with HZO, she was treated with antiviral agents, antiplatelet drugs, steroid and stellate ganglion block. Those irregularities were found to diminish on the sequential angiograms, and the aneurysm disappeared four month later.

[Crossed cerebellar diaschisis in putaminal hemorrhage--evaluation by the Xe-133 clearance method].

Metabolic depression in the contralateral cerebellar hemisphere caused by a supratentorial lesion is called crossed cerebellar diaschisis (CCD). In order to investigate diaschisis based on the location and extension of lesions, time course and prognosis, 31 patients with putaminal hemorrhage were examined by the Xe-133 clearance method (67 studies in all). They consisted of 20 males and 11 females, from 40 to 77 years old (mean: 57.1 +/- 8.9). Small hematomas (mean volume: 16.1 +/- 8.4 ml) in 18 patients were treated nonsurgically, whereas medium and large hematomas (mean volume: 57.5 +/- 29.9 ml) in 13 patients were treated by craniotomy for evacuation. rCBF was measured using a BI 1400 rCBF Analyzer (Valmet, Denmark), and CCD was considered positive when the percentage difference in cerebellar blood flow was 10.1% (mean + 2SD) greater than obtained in 21 normal controls. CCD was observed in 10 patients (55.6%) in the non-surgical group and in 9 patients (69.2%) in the surgical group. In the non-surgical group, CCD was positive in 5 of the 7 cases (71.4%) involving the posterior limb of the internal capsule and in 7 of the 11 cases (63.6%) involving the corona radiata. The surgical group was divided into three types based on the time course of CCD after surgery, i.e., type A: persistent CCD found two months later, type B: postoperative CCD had resolved two months later, and type C: no CCD observed after surgery. Mean hematoma volume was significantly greater in type A (79.0 +/- 19.8 ml) than in type B (44.6 +/- 8.5 ml) or type C (30.7 +/- 3.7 ml) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of p53 gene mutations in low- and high-grade astrocytomas by polymerase chain reaction-assisted single-strand conformation polymorphism and immunohistochemistry.

Using polymerase chain reaction-assisted single-strand conformation polymorphism (PCR-SSCP) and immunohistochemical analyses, mutations in the p53 tumor suppressor gene were examined in 19 low- and high-grade gliomas. By PCR-SSCP and nucleotide analyses, p53 gene mutation was seen in 7 gliomas. Out of the 7 mutations, 3 were located at the CpG site of the previously proposed hot-spot codons 248 and 273, 2 were at codons 171 and 214 and the other 2 were in intron 5, 1 at the splice acceptor site and the other in the vicinity of the splice donor site. The latter 4 mutations have not, or only rarely, been observed in gliomas or in other tumors. However, their effect on the structural and functional alteration of the p53 protein was suggested by positive intranuclear p53 immunostaining in neoplastic cells in 3 mutations including the 1 at the splice acceptor site. In connection with glioma grading, the p53 gene mutation was shown to have occurred in both low- and high-grade gliomas, often in most of the neoplastic cells, as suggested by lack of distinct normal bands and ladders in SSCP and direct sequencing, respectively. The absence of recurrence and malignant transformation over a considerably long postoperative time in our low-grade glioma cases suggested that the p53 gene mutation might not be sufficient for the progression from low- to high-grade gliomas. The frequency of detection of mutation was 7/19(37%) by PCR-SSCP, 8/19(42%) by immunohistochemistry and 10/19(53%) by both methods. The results of PCR-SSCP and immunohistochemistry were consistent in 14 cases (73.7%), but not in 5 cases(26.3%).(ABSTRACT TRUNCATED AT 250 WORDS)