Gamma oscillation underlies hyperthermia-induced epileptiform-like spikes in immature rat hippocampal slices.

BACKGROUND: Recently a hyperthermic rat hippocampal slice model system has been used to investigate febrile seizure pathophysiology. Our previous data indicates that heating immature rat hippocampal slices from 34 to 41 degrees C in an interface chamber induced epileptiform-like population spikes accompanied by a spreading depression (SD). This may serve as an in vitro model of febrile seizures. RESULTS: In this study, we further investigate cellular mechanisms of hyperthermia-induced initial population spike activity. We hypothesized that GABA(A) receptor-mediated 30-100 Hz gamma oscillations underlie some aspects of the hyperthermic population spike activity. In 24 rat hippocampal slices, the hyperthermic population spike activity occurred at an average frequency of 45.9 +/- 14.9 Hz (Mean +/- SE, range = 21-79 Hz, n = 24), which does not differ significantly from the frequency of post-tetanic gamma oscillations (47.1 +/- 14.9 Hz, n = 34) in the same system. High intensity tetanic stimulation induces hippocampal neuronal discharges followed by a slow SD that has the magnitude and time course of the SD, which resembles hyperthermic responses. Both post-tetanic gamma oscillations and hyperthermic population spike activity can be blocked completely by a specific GABA(A) receptor blocker, bicuculline (5-20 microM). Bath-apply kynurenic acid (7 mM) blocks synaptic transmission, but fails to prevent hyperthermic population spikes, while intracellular diffusion of QX-314 (30 mM) abolishes spikes and produces a smooth depolarization in intracellular recording. CONCLUSION: These results suggest that the GABA(A) receptor-governed gamma oscillations underlie the hyperthermic population spike activity in immature hippocampal slices.

Diagnostic yield of brain biopsy in neurodegenerative disorders.

OBJECTIVE: The diagnostic yield and therapeutic implications of brain biopsy were determined in a series of 50 consecutive brain biopsies that were performed in 48 patients between 1990 and 1995 at The Johns Hopkins Hospital to assess progressive neurodegenerative disorders of unclear origin. METHODS: Severely immunocompromised patients and patients undergoing biopsies for suspected neoplastic lesions were excluded from this analysis. Before surgery, the patients had undergone extensive laboratory and radiographic tests, including lumbar puncture (all 48 patients), electroencephalography (26 of 48 patients), magnetic resonance imaging (all 48 patients), and angiography (17 of 48 patients). Despite the results of these studies, diagnoses could not be established, and thus, brain biopsies were undertaken. RESULTS: Only 10 of the 50 biopsies (44 open procedures and 6 stereotactic procedures) led to diagnoses, resulting in a diagnostic yield of 20%. An additional three biopsies (6%) were only suggestive of diagnoses. The results of 33 biopsies (66%) were abnormal but nonspecific, and the results of 4 (8%) were normal. Minor complications associated with biopsy occurred in five cases (10%), and there were no deaths. Of the 10 patients whose biopsies were diagnostic, only 4 underwent meaningful therapeutic intervention as a result of the procedure, resulting in an overall therapeutic benefit in only 8% of all the cases. An analysis of patient subgroups to elucidate a correlation with diagnostic biopsy revealed that patients with focal magnetic resonance imaging findings had the highest likelihood of a diagnostic biopsy (odds ratio, 4.00). Electroencephalography and laboratory abnormalities were not predictive of a diagnostic biopsy. CONCLUSION: We conclude that the current diagnostic yield (20%) of brain biopsy for progressive neurodegenerative disorders is lower than that of earlier reports and that the therapeutic benefits of the procedure are limited.

Hemispherectomy: a hemidecortication approach and review of 52 cases.

Between 1975 and 1994, 52 hemispherectomies, of which two were anatomical and 50 hemidecortications, were performed at Johns Hopkins Medical Institutions. Eighteen patients were 2 years old or less. There were three perioperative mortalities and one patient died 9 months later from causes not related to surgery. One patient developed hydrocephalus 6 years postsurgery and has been treated effectively. Seizure control and the functional status of each patient were measured as outcome variables. Forty-six (96%) of the surviving patients were seizure free or had reduced seizures as of their last follow-up examination. Twenty-one individuals (44%) were participating in age-appropriate classes or working independently, 18 were classified as semiindependent, and nine children will likely depend on a lifetime of assisted living. The relationships between the outcome variables and the patient's age at surgery, the interval to surgery, and the etiology of the disease were compared. The authors' clinical experiences strongly suggest the importance of a multidisciplinary approach to patient selection and follow-up care. Moreover, anesthetic management of infant surgery is a major component of success.

The role of cerebral revascularization in patients with intracranial aneurysms.

Cerebral revascularization offers an important adjunct to parent-vessel ligation in the treatment of large and otherwise inaccessible intracranial aneurysms. Good or excellent outcomes can be expected in approximately 80% of patients. Poor outcomes and ischemic complications were highest in posterior circulation lesions. Cranial neuropathies from mass effect associated with giant aneurysms of the cavernous and intradural internal carotid artery will improve and be cured in the majority of patients treated with universal revascularization approach. In combination with open parent vessel ligation or endovascular occlusion, durable protection from subarachnoid hemorrhage can be achieved.

Treatment of posterior third ventricular central neurocytoma with endoscopic biopsy, endoscopic third ventriculostomy and stereotactic radiosurgery.

Central neurocytomas of the posterior third ventricle are rare. These typically benign lesions have recently been shown to respond well to Gamma knife stereotactic radiosurgery (SRS). We present the case of a posterior third ventricle central neurocytoma presenting with aqueduct obstruction. The patient was treated with endoscopic biopsy and endoscopic third ventriculostomy, followed by Gamma knife radiosurgery. At 2 years the tumor has diminished in size and the patient is neurologically intact. This treatment strategy may avoid the risk of open ventricular surgery and the need for shunts in patients with central neurocytomas of appropriate size and location.