AMPA receptor alterations precede mossy fiber sprouting in young children with temporal lobe epilepsy.

Following neurological injury early in life numerous events, including excitotoxicity, neural degeneration, gliosis, neosynaptogenesis, and circuitry reorganization, may alone or in concert contribute to hyperexcitability and recurrent seizures in temporal lobe epilepsy. Our studies provide new evidence regarding the temporal sequence of key elements of hippocampal reorganization, mossy fiber sprouting and glutamate receptor subunit up-regulation, in a subset of young temporal lobe epileptic patients. Without evidence of mossy fiber sprouting, the youngest age group (3-10 years old) of mesial temporal lobe epileptic patients demonstrated enhanced glutamate receptor subunit profiles, suggesting that the dendritic change precedes axonal sprouting. However, sclerotic hippocampal specimens from epileptic patients ages 12-15 years old had the characteristic features of glutamate receptor up-regulation and mossy fiber sprouting first identified in the adult, indicating that reconstructed circuits appear early in the course of the disease. Non-sclerotic hippocampal specimens from lesion associated temporal lobe epileptic patients of all age groups showed minimal cell loss, sparse staining of glutamate receptor subunits in the dentate gyrus, and little or no mossy fiber sprouting. These compelling findings suggest a progressive sequence of events in the reorganization of the dentate gyrus of sclerotic hippocampal specimens. We suggest that cell loss and up-regulation of glutamate receptor subunits appear early in temporal lobe epilepsy and contribute to the synaptic plasticity that may facilitate the subsequent sprouting of mossy fiber collaterals which compound an already precipitous state of decline. The combination of pre-synaptic and post-synaptic changes serves as a potential substrate for hyperexcitability.

Predicting verbal memory decline following anterior temporal lobectomy (ATL).

OBJECTIVE: To develop a multivariate risk factor model for predicting postoperative verbal memory decline in an individual patient following dominant or nondominant anterior temporal lobectomy (ATL). METHODS: The authors studied 132 consecutive ATL patients who 1). were older than 16 years at surgery, 2). had estimated preoperative Full Scale IQ score of >69, 3) had unilateral language dominance based on the intracarotid amobarbital procedure (IAP), and 4) underwent neuropsychological testing at baseline and >or=6 months postoperatively (mean 1.2 years). Five potential risk factors for postoperative verbal memory decline were selected a priori that reflect the functional adequacy of the to-be-resected temporal lobe. These were 1). resection in the dominant hemisphere, 2). MRI findings other than exclusively unilateral mesial temporal sclerosis, intact preoperative 3). immediate and 4). delayed verbal memory function, and 5). intact IAP memory performance following injection contralateral to the seizure focus. Verbal memory decline was defined using two verbal memory tests and published reliable change indices. RESULTS: Thirty-eight percent of the sample declined reliably on one or both verbal memory measures. Logistic regression analysis demonstrated that all five risk factors were significantly and independently associated with outcome, with side of surgery having the strongest association (p < 0.0001) and preoperative immediate verbal memory the weakest (p < 0.05). CONCLUSIONS: An individual patient's risk for postoperative verbal memory decline following dominant or nondominant ATL can be predicted using clinical data routinely available preoperatively (side of surgery, qualitative MRI, baseline memory testing, IAP performance). This information may be useful for preoperative patient counseling.

Fibro-osseous lesions of the central nervous system: report of four cases and literature review.

Fibro-osseous lesions, also reported as calcifying pseudoneoplasms of the neural axis, are uncommon lesions of the CNS. We report four additional cases: two extraaxial and two intraaxial, in patients ages 33, 47, 49, and 59 years at presentation. Fibro-osseous lesions involving the CNS demonstrate variable proportions of fibrous stroma, bone, palisading spindle to epithelioid to multinucleated cells in association with a highly distinctive, perhaps pathognomonic, chondromyxoid-like matrix often distributed in a nodular pattern. This histopathologically distinctive lesion can be seen in many regions of the neuraxis, often with a dural association, and most commonly along the vertebral column. It appears to be a slow-growing lesion and, with wide excision, the prognosis is excellent. The etiology remains unclear, but the preponderance of data favors a reactive rather than neoplastic process. If this putative pseudotumor is not recognized histopathologically, a neoplastic or infectious differential might result in inappropriate investigations and potentially harmful therapies.

Fibro-osseous lesions involving the brain: MRI.

We present the MRI findings in two patients with "fibro-osseous lesions" involving the central nervous system. A left temporal lobe mass was present in one patient and an extra-axial mass at the skull base in the other. In both cases, calcification was present, with low signal intensity on T1- and T2-weighted images.

Cervical spinal meningioma with unusual MR contrast enhancement.

A 16-year-old girl had progressive neck pain and weakness in the left hand. MR images showed a dumbbell-shaped spinal tumor with a prominently enhancing intradural component and a minimally enhancing extradural component. Pathologic examination revealed a meningioma with an intradural transitional component and an extradural syncytial component. The tumor showed no significant cystic change or necrosis.

Malignant ependymomas in a patient with Turcot's syndrome: case report and management guidelines.

BACKGROUND: Turcot's Syndrome is the association of multiple adenomatous polyps of the colon with a primary tumor of the central nervous system. We present the first reported case of Turcot's Syndrome in a patient with malignant ependymomas. Recent advances in the elucidation of the genetic basis for the hereditary forms of colon cancer have provided a clearer understanding of the etiology of Turcot's Syndrome. This new information is relevant to the neurosurgical community and provides updated guidelines in the diagnosis and management of patients with this complex disease process. RESULTS: Turcot's Syndrome is related to two distinct genetic errors. The first involves a germ-line mutation in the adenomatous polyposis coli (APC) gene, which is postulated to act as a tumor suppressor gene. The second is a germ-line defect in one of a group of genes responsible for DNA nucleotide mismatch repair. CONCLUSION: The elucidation of the gene defects responsible for the hereditary forms of colon cancer has provided a clearer understanding of the molecular basis of Turcot's Syndrome. Patients with hereditary forms of colon cancer and neurologic symptoms require immediate and thorough investigation because of their significantly increased risk of developing CNS tumors. Previously healthy patients diagnosed with a CNS tumor with a family history of adenomatous polyposis coli should undergo screening and surveillance colonoscopy as the CNS lesion may precede colonic symptoms. CNS screening guidelines for asymptomatic patients with adenomatous polyposis coli requires further risk analysis studies. All patients diagnosed with Turcot's Syndrome should be tested for the gene defect, including the CNS tumor tissue to provide further data on the genetic relationship between Turcot's Syndrome and the hereditary forms of colon cancer.

Failure of standard magnetic resonance imaging in patients with refractory temporal lobe epilepsy.

OBJECTIVE: To compare the sensitivity of standard magnetic resonance imaging (MRI) scans done outside an epilepsy center with that of special protocol MRI scans done at an epilepsy center in delineating relevant lesions of the temporal lobe. SUBJECTS: Eighty-four consecutive patients who had temporal lobe resections for refractory temporal lobe epilepsy between January 1, 1993, and February 1, 1996. DESIGN: The reports of findings on standard MRI scans done outside an epilepsy center were compared with the findings of special protocol MRI scans done with 1.5-mm T1-weighted coronal and 3-mm T2-weighted coronal images (no gaps) on a 1.5-T system. Both sets of MRI findings were compared with findings on histologic examination of the resected tissue. RESULTS: Of the 84 patients, 51 had standard MRI scans done outside an epilepsy center; of these, there were 34 patients with normal results, 10 with tumors, 2 with vascular malformations, 2 with hippocampal atrophy, 2 with unclassified abnormalities, and 1 with cortical malformation. In 32 of the 34 patients with normal results of an MRI scan done outside an epilepsy center, abnormalities were found on our special protocol MRI scans. These included hippocampal atrophy in 27 patients, tumors in 2, and cortical malformations in 1. Additionally, all 17 of the abnormalities detected on the standard MRI scans done outside the epilepsy center were identified on our special protocol MRI scans. Important pathologic abnormalities of the temporal lobe were identified in 16 (35%) of the 46 patients with standard MRI scans done outside an epilepsy center and in 44 (96%) with our special protocol MRI scans. In the 29 patients for whom adequate surgical specimens were available and results of standard MRI scans were normal, our special protocol MRI scans showed the abnormality in 27 (93%). CONCLUSIONS: Conventional neuroimaging studies are inadequate for diagnosing hippocampal sclerosis although they fairly readily detect low-grade tumors and vascular malformations. Magnetic resonance imaging scans for the evaluation of patients with refractory temporal lobe epilepsy should be done with a special temporal lobe protocol and read by physicians experienced with the findings in hippocampal sclerosis. Health care dollars are wasted on neuroimaging done for refractory temporal lobe epilepsy outside epilepsy centers.

Low initial tau phosphorylation in human brain biopsy samples.

A rapid reversible tau phosphorylation at Ser 396/404 was observed in adult human cortical biopsy tissue and rat primary cortical cell cultures. Tau phosphorylation increased usually during the first 20-30 min in phosphate-buffered saline, followed by a decrease. The time course of tau phosphorylation and dephosphorylation in biopsy tissue could be lengthened by culturing in defined, oxygenated medium, instead of in phosphate-buffered saline. Phosphorylation of total protein in biopsy tissue occurred in two phases, with peaks at 30 and 90 min. The first peak of total protein phosphorylation coincided with the peak of tau phosphorylation, although both the first and second peaks of total protein phosphorylation coincided with the first and second peaks of neurofilament-H phosphorylation.

Multiple ependymomas in a patient with Turcot's syndrome.

A 21-year-old woman was diagnosed with Turcot's syndrome (TS) at age 16 years. She had two ependymomas, one was located in the left middle cerebellar peduncle and the other in the low sacral spinal canal. Her mother and brother both had colectomies for colonic polyposis. Her maternal uncle and grandfather also had this disease and both died from cancer of the colon in their fourth decade of life. The patient was found to have hyperpigmented spots in the retina, skull osteomas and normal neurological examinations. The bone scan and CSF were normal and she had a germline mutation in the segment 3 of the adenomatous polyposis coli (APC) gene. Following partial resection of the two ependymomas, she was treated with radiation and chemotherapy. One year after surgery, paraspinal desmoid tumors were found and removed. She is presently 42 months postsurgical resection of the neural tumors and has remained central nervous system tumor-free. The occurrence of multiple ependymoma in TS has not been reported, and the control of this patient's ependymomas is consistent with other reports of long-term survival with TS and glial tumors.

Adrenocorticotropic hormone immunoreactivity in the hippocampal formation of temporal lobe epilepsy patients.

PURPOSE: We wished to identify immunocytochemically the distribution of proopiomelanocortin-related peptides in the hippocampal formation of patients with epilepsy. METHODS: Surgical hippocampal specimens from temporal lobe epilepsy (TLE) patients and autopsy control tissue were examined immunocytochemically for ACTH, alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. RESULTS: There was a dense distribution of ACTH-immunoreactive neurons in the hippocampal formation of patients with mesial TLE syndrome (MTLE). These hippocampal specimens showed significant cell loss. ACTH-positive neurons were most prominent in the subiculum, with scattered ACTH-immunoreactive neuronal elements distributed in the cornu ammonis fields and hilus. Light ACTH immunoreactivity was detected in the tumor-related epileptic hippocampal specimens, which showed minimal cell loss. Although autopsy control tissue from the hypothalamus showed intense ACTH staining patterns in cells and fibers, there was little or no ACTH immunoreactivity in the autopsy hippocampal tissue. The expression of ACTH immunoreactive elements was correlated with patterns of cell loss. No alpha-MSH- or beta-endorphin-immunoreactive neurons were detected in any of the hippocampal specimens. CONCLUSIONS: ACTH has anticonvulsant properties, and its novel expression in the glutamatergic subicular neurons, which provide the main outflow of the hippocampal formation, may represent an attempt by the damaged hippocampal circuit to restore the balance of excitatory/inhibitory neurotransmission in TLE.

Distribution of AMPA receptor subunits in the hippocampal formation of temporal lobe epilepsy patients.

The immunocytochemical distribution of the AMPA-selective receptor subunits GluR1 and GluR2/3 were mapped in the human hippocampal formation obtained from surgery for medically intractable temporal lobe epilepsy. GluR2/3 immunoreactivity was detected in all principal cell types of the hippocampal formation, including hilar neurons, granule cells of the dentate gyrus, and pyramidal cells of the cornu ammonis fields and subiculum. GluR2/3 immunostaining typically filled the cell bodies and processes of neurons. A comparison of GluR2/3 immunoreactivity in a sclerotic specimen versus a non-sclerotic specimen demonstrated a profound loss of staining, specifically in the areas where neuronal dropout was occurring, including CA1, CA3 and the hilus. An analysis of GluR1 immunoreactivity in non-sclerotic specimens revealed that it was predominantly localized to cellular processes throughout the cornu ammonis fields, with a sparse staining of the dentate gyrus outer molecular layer and little to no staining of the dentate gyrus inner molecular layer. Similar to the GluR2/3-immunostained patterns, GluR1 immunoreactivity was lost in the cornu ammonis fields of sclerotic hippocampal specimens, corresponding to patterns of neuronal dropout. Our most compelling finding was a unique extensive pattern of GluR1 and Glu2/3 immunoreactivity throughout the molecular layers of the dentate gyrus of severely compromised hippocampi. The altered staining of GluR1 and GluR2/3 complements some of the patterns of axonal sprouting already described for the dentate gyrus, with a conjecture that their anatomy and distribution pattern underlies to some degree the reorganization of the sclerotic hippocampus. A combination of enhanced glutamatergic transmission and changes in neuropeptides that modulate hippocampal circuitry could greatly affect the degree of excitability in the hippocampal formation. The alterations of GluR1 and GluR2/3 immunoreactivity in the dentate gyrus add another component to the concept of reorganization in the epileptic sclerotic hippocampus.

Assessing myocardial viability to help select patients for revascularization to improve left ventricular dysfunction due to coronary artery disease.

Left ventricular dysfunction has become one of the most common causes of death, disability, and health care costs. Left ventricular dysfunction is usually due to coronary artery disease (CAD) and can be improved considerably by successful revascularization in many, but not all, patients. The key issue determining whether revascularization will relieve left ventricular dysfunction is whether the patient has enough viable myocardium to improve after revascularization. Viable myocardium is located anatomically in the subepicardial layers of the left ventricular wall, above the infarct in the subendocardial layers in the distribution of a stenotic coronary artery. Clinical history, physical examination, resting or exercise ECG, and imaging studies of left ventricular function often fail to distinguish patients with viable myocardium. Thallium-201 myocardial imaging at stress and rest is better if performed with reinjection of thallium-201 at rest, but this method still misses many patients with viable myocardium. Positron emission tomographic (PET) myocardial imaging to compare distributions of a perfusion tracer versus a metabolic tracer (fluorine-18-fluoro-deoxyglucose, 18FDG) has been cited as the "gold standard" method to identify viable myocardium by position papers from several professional organizations. PET imaging of rubidium-82, a potassium analogue ("washout" from "early" [first 1.5 minutes] to "late" [next 5 minutes] images) and gated magnetic resonance imaging (MRI) also show promise.

Absence of defects in SPECT thallium-201 myocardial images in patients with systemic hypertension and left ventricular hypertrophy.

Hypertension is common in patients undergoing stress and delayed single-photon emission computed tomography (SPECT) thallium-201 myocardial perfusion imaging. Investigators have reported that patients with end-stage renal disease and left ventricular hypertrophy due to hypertension have diminished lateral/septal count ratios on stress and delayed imaging mimicking lateral myocardial infarction in approximately 35% of patients. Subsequently, hypertension has been cited as a frequent cause of thallium-201 artifacts. The purpose of this study was to compare myocardial SPECT thallium-201 distribution in a broader group of patients with left ventricular hypertrophy resulting from hypertension with normal file subjects in order to determine the prevalence of abnormal studies and to compare the lateral/septal count ratio. Average counts in all myocardial regions in the male study group (n = 16) were compared with those in the normal male file patients (n = 49), with particular attention to the lateral and septal walls. In the group of 16 men with hypertension and left ventricular hypertrophy, as a whole, the mean lateral/septal wall count ratio was 4.4% lower (1.09 +/- 0.07) than that in the normal file (1.14 +/- 0.07; p < 0.01). At 3-hour delay, the ratio was virtually the same in the study group (1.06 +/- 0.09) as in the normal file (1.08 +/- 0.06; p = NS). Most important, for clinical purposes no patient had a defect, defined as a lateral/septal count ratio > 2.0 SD below normal limits. All thallium-201 studies were interpreted as normal. In conclusion, myocardial thallium-201 distribution is normal in patients with left ventricular hypertrophy due to hypertension.

Osteoma of the frontoethmoidal sinus with secondary brain abscess and intracranial mucocele: case report.

The authors report the case of a 17-year-old patient with an osteoma of the frontoethmoidal sinus who had a secondary abscess of the frontal lobe and an intracranial mucocele. Clinical, radiological, and surgical correlates of this triad are presented.

Nuclear factor-kappa B in rat brain: enhanced DNA-binding activity following convulsant-induced seizures.

The DNA-binding protein nuclear factor-kappa B (NF-kappa B) is a pleiotropic transcription factor which regulates the transcription of specific target genes such as cytokines. The existence of NF-kappa B has not been reported in brain tissue. This is the first report demonstrating the expression of NF-kappa B in the rat brain. After pentylene tetrazole (s.c.)-induced clonic-tonic seizures at an LD50 dose of 85 mg/kg, we have shown a gradual increase in NF-kappa B expression reaching a maximum at 24 h, a decrease at 48 h and again increased at 96 and 120 h. A similar time-dependent pattern was observed for the NF-kappa B subunit p50 expression. The NF-kappa B subunit p65 was not expressed at all. These data suggest a possible underlying mechanism of signal transduction and transcriptional regulation of late-response genes after perturbations in the CNS milieu.

Intraoperative electrocorticography during tumor resection: impact on seizure outcome in patients with gangliogliomas.

Gangliogliomas are indolent neoplasms that are often associated with long-standing intractable seizures. The seizure-free outcome following ganglioglioma resection alone (or "lesionectomy") has been generally favorable, ranging in most series from 50% to 65%. Thus, the value of resection of epileptogenic cortex in addition to tumor with regard to seizure outcome has been the subject of controversy. The authors describe a series of 12 patients with frontal or temporal lobe gangliogliomas associated with long-standing intractable seizures. In these patients, intraoperative electrocorticography was used to guide the resection of epileptogenic cortex along with tumor. Functional brain mapping, interictal and ictal monitoring of seizures, as well as thorough neuropsychological assessments were performed prior to resection in all cases. Outcome with regard to seizures, tumor recurrence, and neurological deficits was assessed with a mean follow-up period of 3.1 years. There was universal freedom from seizures postoperatively in 11 patients in whom complete or near-complete resection of epileptogenic cortex was achieved. In one patient in whom complete tumor resection and subtotal removal of epileptogenic cortex was achieved, a 95% reduction in seizure frequency was identified. No tumor recurrence or neurological deficits were observed. In a subset of four patients, neuropsychological and cognitive function were evaluated pre- and postoperatively. In these four, a clear trend toward improvement was noted in most functions. Thus, resection of epileptogenic cortex along with tumor may improve seizure outcome in selected patients with tumor-associated epilepsy without engendering identifiable neurological or cognitive deficits attributable to the incremental resection.