Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Clinical outcomes after stereotactic radiosurgery for idiopathic trigeminal neuralgia.

OBJECT: Stereotactic radiosurgery is an increasingly used and the least invasive surgical option for patients with trigeminal neuralgia. In this study, the authors investigate the clinical outcomes in patients treated with this procedure. METHODS: Independently acquired data from 220 patients with idiopathic trigeminal neuralgia who underwent gamma knife radiosurgery were reviewed. The median age was 70 years (range 26-92 years). Most patients had typical features of trigeminal neuralgia, although 16 (7.3%) described additional atypical features. One hundred thirty-five patients (61.4%) had previously undergone surgery and 80 (36.4%) had some degree of sensory disturbance related to the earlier surgery. Patients were followed for a maximum of 6.5 years (median 2 years). Complete or partial relief was achieved in 85.6% of patients at 1 year. Complete pain relief was achieved in 64.9% of patients at 6 months, 70.3% at 1 year, and 75.4% at 33 months. Patients with an atypical pain component had a lower rate of pain relief (p = 0.025). Because of recurrences, only 55.8% of patients had complete or partial pain relief at 5 years. The absence of preoperative sensory disturbance (p = 0.02) or previous surgery (p = 0.01) correlated with an increased proportion of patients who experienced complete or partial pain relief over time. Thirty patients (13.6%) reported pain recurrence 2 to 58 months after initial relief (median 15.4 months). Only 17 patients (10.2% at 2 years) developed new or increased subjective facial paresthesia or numbness, including one who developed deafferentation pain. CONCLUSIONS: Radiosurgery for idiopathic trigeminal neuralgia was safe and effective, and it provided benefit to a patient population with a high frequency of prior surgical intervention.

Subnecrotic stereotactic radiosurgery controlling epilepsy produced by kainic acid injection in rats.

OBJECT: Any analysis of the potential role of stereotactic radiosurgery for epilepsy requires the experimental study of its potential antiepileptogenic, behavioral, and histological effects. The authors hypothesized that radiosurgery performed using subnecrotic tissue doses would reduce or abolish epilepsy without causing demonstrable behavioral side effects. The kainic acid model in rats was chosen to test this hypothesis. METHODS: Chronic epilepsy was successfully created by stereotactic injection of kainic acid (8 microg) into the rat hippocampus. Epileptic rats were divided into three groups: high-dose radiosurgery (60 Gy, 16 animals), low-dose (30 Gy, 15 animals), and controls. After chronic epilepsy was confirmed by observation of the seizure pattern and by using electroencephalography (EEG), radiosurgery was performed on Day 10 postinjection. Serial seizure and behavior observation was supplemented by weekly EEG sessions performed for the next 11 weeks. To detect behavioral deficits, the Morris water maze test was performed during Week 12 to study spatial learning and memory. Tasks involved a hidden platform, a visible platform, and a probe trial. After radiosurgery, the incidence of observed and EEG-defined seizures was markedly reduced in rats from either radiosurgically treated group. A significant reduction was noted after high-dose (60 Gy) radiosurgery in Weeks 5 to 9 (p < 0.003). After low-dose (30 Gy) radiosurgery, a significant reduction was found after 7 to 9 weeks (p < 0.04). During the task involving the hidden platform, kainic acid-injected rats displayed significantly prolonged latencies compared with those of control animals (p < 0.05). Hippocampal radiosurgery did not worsen this performance. The probe trial showed that kainic acid-injected rats that did not undergo radiosurgery spent significantly less time than control rats in the target quadrant (p = 0.03). Rats that had undergone radiosurgery displayed no difference compared with control rats and demonstrated better performance than rats that received kainic acid alone (p = 0.04). Radiosurgery caused no adverse histological effects. CONCLUSIONS: In a rat model, radiosurgery performed with subnecrotic tissue doses controlled epilepsy without causing subsequent behavioral impairment.

Brain metastases in patients with no known primary tumor.

BACKGROUND: The care of patients with a brain metastasis from unknown primary site is controversial. The authors reviewed the results of stereotactic radiosurgery in this group of patients to better define clinical expectations. METHODS: During an 11-year interval, radiosurgery was performed in 421 patients with brain metastases at the University of Pittsburgh. Fifteen patients had solitary or multiple (< or = 5) brain metastases without a detectable primary site at the time of initial presentation. In five patients, a histologic diagnosis of cancer was obtained from extracranial metastatic sites. In 10 patients, a diagnosis was obtained from the brain. A total of 31 tumors with a mean volume of 4.3 mL (range, 0. 05-18.6 mL) underwent radiosurgery with a mean marginal dose of 16.2 Gray (Gy) (range, 12-20 Gy). Fourteen patients (93.3%) also received whole brain fractionated radiation therapy. RESULTS: The median survival was 15 months after radiosurgery (range, 1-48 months) and 27 months after their initial diagnosis of cancer. In 4 patients (26. 7%), the primary tumor was discovered later (lung in 3 patients and liver in 1). Three of these four patients died due to progression of their primary tumor. Of the remaining 11 patients, 4 died of progression of extracranial metastases, 2 died of other systemic diseases, and 3 patients died because of progression of brain metastasis. Three patients (20%) were still living between 21-48 months after radiosurgery. The presence of active systemic disease and brain stem location both were associated with a poor outcome (P = 0.004 and 0.04). The actuarial imaging-defined local tumor control rate was 91.3 +/- 5.9% at 4 years. CONCLUSIONS: Radiosurgery was an effective strategy for patients with brain metastases from an unknown primary site. Disease progression outside of the brain was the usual cause for patient death.

Repeated radiosurgery for incompletely obliterated arteriovenous malformations.

OBJECT: The goal of this study was to define treatment results of repeated arteriovenous malformation (AVM) radiosurgery, namely AVM obliteration and complications. METHODS: The authors analyzed their experience with repeated AVM radiosurgery performed in 41 patients for whom follow-up review lasted at least 2 years. The median duration of follow up was 34 months (range 7-65 months) after repeated radiosurgery in this group. The residual nidus was located within the area of focus (in field) of the initial radiosurgery in 28 patients (68%). Initial doses to the margin varied from 12.5 to 20 Gy (median 18 Gy). During repeated treatment the dose to the margin varied from 12.5 to 20 Gy (median 17 Gy) and the retreated volumes ranged from 0.4 to 7 cm3 (median 2.1 cm3). Follow-up angiography performed at least 2 years postradiosurgery revealed complete AVM obliteration in 21 (70%) of 30 patients. The estimated overall 2-year obliteration rate, based on findings on magnetic resonance imaging (eight of 11 obliterated) and angiography (29 of 41 obliterated) was 71%. Obliteration rates correlated with margin doses (p = 0.0045) with a trend toward higher rates in cases with in-field nidus persistence (p = 0.0637). The dose-response curve for AVM nidus obliteration was not significantly different from that of the initial radiosurgery. In two patients (5%) intracranial AVM hemorrhage developed within 125.9 risk years after repeated radiosurgery (1.6% per patient year). Persistent symptomatic adverse radiation effects developed in two (5%) of 41 patients following repeated radiosurgery. Postradiosurgical imaging changes were identified in 11 (27%) of 41 patients, which correlated with a 12-Gy volume from repeated surgery (p = 0.019). CONCLUSIONS: When necessary, repeated AVM radiosurgery achieves obliteration with an acceptable risk. Despite the effects of previous irradiation, repeated radiosurgery required similar or slightly higher radiation doses to achieve the same in-field obliteration rates as those needed to obliterate an AVM that had not been treated by radiation previously.

Histological effects of trigeminal nerve radiosurgery in a primate model: implications for trigeminal neuralgia radiosurgery.

OBJECTIVE: Stereotactic radiosurgical treatment of the proximal trigeminal nerve is used to relieve the pain of trigeminal neuralgia. The mechanism of the radiosurgical effect is not understood. METHODS: Two adult baboons underwent stereotactic magnetic resonance imaging-guided radiosurgery, using a gamma knife. A single 4-mm isocenter was targeted to each proximal trigeminal nerve, just anterior to the pons, to deliver a maximal dose of 80 or 100 Gy (total of four nerves). A nonirradiated baboon brain and nerves served as control specimens. Six months after treatment, magnetic resonance imaging was again performed and the brains and nerves were studied using light and electron microscopy. RESULTS: Magnetic resonance imaging indicated a 4-mm-diameter area of contrast enhancement at the target site in each nerve. All irradiated nerves exhibited axonal degeneration and mild edema at the target, with remnants of some myelinated axons. Large and small myelinated and unmyelinated fibers were affected. No inflammation was observed. Nerve necrosis was identified after 100-Gy treatment. The trigeminal ganglion appeared normal. CONCLUSION: Radiosurgery at 80 Gy causes focal axonal degeneration of the trigeminal nerve. At higher doses, partial nerve necrosis is observed. We think that these effects influence the physiological features of trigeminal neuralgia.

Stereotactic radiosurgery for management of deep brain cavernous malformations.

The indications for stereotactic radiosurgery for patients with cavernous malformations of the brain are discussed. Specific reference is made to technique and dose selection and to the results and potential complications of this approach. Radiosurgery is an alternative to microsurgical resection for some patients with malformations in high-risk brain locations.

The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia.

Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.

[Neurinoma arising from the first branch of the trigeminal nerve: a case report].

A case of a neurinoma arising from the first branch of the trigeminal nerve in a 40-year-old female is reported. The patient was admitted with the chief complaint of loss of Lt. visual acuity and mild hypoesthesia in the area of the first branch of the trigeminal nerve. A CT scan and MRI revealed a tumor extending through the superior orbital fissure into the orbita. Subtotal resection of the tumor was performed by a fronto-orbito-zigomatic approach and a histological diagnosis of neurinoma was made. Although the hypoesthesia remained, the visual acuity was markedly improved postoperatively. A neurinoma arising from the first branch of the trigeminal nerve is very rare. To our knowledge, including our case, only five cases which were described for clinical and diagnostic features and surgical management have been reported. There were three males and two females, and the age ranged from 1 to 57 years. Neurologically, all cases presented hypoesthesia in the area of the first branch of the trigeminal nerve and exophthalmus on admission. Visual disturbance was found in three cases. Radiologically, the enlargement of the superior orbital fissure was revealed in two cases. Angiography performed in three cases demonstrated the avascular mass. Three patients received CT scan and only the present case used MR imaging. Surgical resection was performed in all cases through various approaches. The fronto-orbito-zygomatic approach which was chosen in our case was useful for obtaining a sufficient operative view. As in our case, excellent outcome was achieved in three other cases due to successful tumor resection.

Effect of glycerol on blood flow distribution in tumoral and peritumoral brain tissue.

The effect of glycerol on blood flow in tumoral and peritumoral tissue was measured in 32 patients with brain tumor, 17 gliomas and 15 meningiomas. Blood flow before and after the administration of glycerol was measured by stable xenon-enhanced computed tomography. The tumor part of glioma was significantly hypoperfused. In contrast, the tumor part of meningioma was significantly hyperperfused. Peritumoral edema of both glioma and meningioma was hypoperfused. After the administration of glycerol, blood flow increased in all regions except for the tumor part of glioma. Vascular responses to glycerol may be different in these two tumor types. The steal phenomena of blood flow might occur in cases of glioma.

[Radiosurgery of cavernous sinus meningiomas with gamma-knife].

The treatment results of cavernous sinus meningioma with gamma-radiosurgery are reported. There were 18 cases of cavernous sinus meningioma, including 2 males and 16 females, whose age ranged from 39 to 63 with an average of 51.0 years. As prior treatments, operative tumor resection or biopsy had been carried out in 14 cases, and the pathology was verified. The other 4 cases were diagnosed clinically with radiological studies. The mean tumor diameter was 28.3mm (17.7-35.0) during the radiosurgery. The maximum dose ranged from 22 to 36Gy (mean 28.0Gy), with the marginal tumor dose ranging from 11 to 18Gy (mean 13.9Gy). Irradiation to the near-by optic nerves was less than 10Gy. Follow-up period ranged from 12 to 50 months with a mean of 25.5 months. MRI showed a minor tumor shrinkage in 9 (50.0%) and no obvious change in 8 (44.4%), and tumor progression in 1 (5.6%), which required a 2nd radiosurgery. Neurologically facial pain and facial dysesthesia were well improved (7/13). However the ophthalmoparesis was usually unchanged and only 1 out of 11 (9.1%) improved after radiosurgery. Deterioration of neurological signs was rare. Symptomatic edema presenting neurological signs was not seen. In conclusion, radiosurgery with a gamma-knife is one of the useful alternatives to operative intervention in the treatment of cavernous sinus meningiomas, not only for tumor control, but also for relief from the symptoms.

[Gamma knife treatment of AVM of the basal ganglia and thalamus].

Arteriovenous malformatios (AVMs) in the basal ganglia (BG) and thalamus (Thal) are difficult to treat by microsurgery or intravascular embolization alone, and the role of stereotactic gamma radiosurgery (gamma knife) of these AVMs is discussed. We have treated 324 cases of AVM with gamma knife since May 1991, and in 71 of these cases (19%) the AVM was in the BG or Thal. The results of gamma radiosurgery on AVMs of the BG and Thal were compared with the results of treating AVMs at other intracranial locations by gamma radiosurgery. The nidi were small (mean diameter: 16.4 mm), and they were treated with a mean maximum dose of 36.4 Gy and marginal dose of 19.9 Gy. The results were evaluated angiographically in 39 (55%) of the 71 cases, with a mean follow-up period of 23 months. The complete obliteration rate of AVMs in the BG and Thal 1 and 2 years after treatment was 54.3% and 92.0%, respectively, and the rate at the other locations was 42.9% and 76.0%, respectively. Adverse effects of this treatment in the AVM cases overall were rebleeding from the nidus in 5 cases (1.5%) and radiation necrosis in 4 cases (1.2%). In conclusion, AVMs of the BG and Thal were effectively and safely treated with the gamma knife, and stereotactic radiosurgery is a definitive alternative treatment for deep seated AVMs.