Modulation of receptive field properties of thalamic somatosensory neurons by the depth of anesthesia.

Modulation of receptive field properties of thalamic somatosensory neurons by the depth of anesthesia. The dominant frequency of electrocorticographic (ECoG) recordings was used to determine the depth of halothane or urethan anesthesia while recording extracellular single-unit responses from thalamic ventral posterior medial (VPM) neurons. A piezoelectric stimulator was used to deflect individual whiskers to assess the peak onset latency, magnitude, probability of response, and receptive field (RF) size. There was a predictable increase in the dominant ECoG frequency from deep stage IV to light stage III-1 anesthetic levels. There was no detectable frequency at stage IV, a 1- to 2-Hz dominant frequency at stage III-4, 3-4 Hz at stage III-3, 5-7 Hz at stage III-2, and a dual 6- and 10- to 13-Hz pattern at stage III-1. Reflexes and other physical signs showed a correlation with depth of anesthesia but exhibited too much overlap between stages to be used as a criterion for any single stage. RF size and peak onset latency of VPM neurons to whisker stimulations increased between stage III-4 and III-1. A dramatic increase in RF size and response latency occurred at the transition from stage III-3 (RF size approximately 2 whiskers, latency approximately 7 ms) to stage III-2 (RF size approximately 6 whiskers, latency approximately 11 ms). Response probability and magnitude decreased from stage III-4 to stage III-3 and III-2. No responses were ever evoked in VPM cells by vibrissa movement at stage IV. These changes in VPM responses as a function of anesthetic depth were seen only when the nucleus principalis (PrV) and nucleus interpolaris (SpVi) trigeminothalamic pathways were both intact. Eliminating SpVi inputs to VPM, either by cutting the primary trigeminal afferent fibers to SpVi or cutting axons projecting from SpVi to VPM, immediately reduced the RF size to fewer than three whiskers. In addition, the predictable changes in VPM response probability, response magnitude, and peak onset latency at different anesthetic depths were all absent after SpVi pathway interruption. We conclude that 1) the PrV input mediates the near "one-to-one" correspondence between a neuronal response in VPM and a single mystacial whisker, 2) in contrast, the SpVi input to VPM is primarily responsible for the RF properties of VPM neurons at light levels of anesthesia and presumably in the awake animal, and 3) alterations in VPM responses produced by changing the depth of anesthesia are due to its selective influence on the properties mediated by SpVi inputs at the level of the thalamus.

Specific matrix metalloproteinase profiles in the cerebrospinal fluid correlated with the presence of malignant astrocytomas, brain metastases, and carcinomatous meningitis.

BACKGROUND: Detection in tumor tissue of specific matrix metalloproteinases (MMPs), particularly gelatinases A and B, correlates with the grade and aggressiveness of primary and metastatic brain tumors. The ability to detect these enzymes in the cerebrospinal fluid (CSF) would be a minimally invasive method of evaluating brain tumors. METHODS: CSF from 66 patients with white blood cell counts of < or = 5 microL were analyzed for the presence of gelatinolytic activity by zymography. Twenty-nine patients had malignant astrocytomas, 10 had brain metastases from systemic malignancies, 4 had systemic cancer not involving the central nervous system, 4 had nonmalignant neurologic diseases, and 19 were healthy controls. Fifteen CSF samples had positive cytologies. The zymographic results were retrospectively correlated with clinical information and CSF cytologic data. RESULTS: CSF from all patients with malignant astrocytomas or brain metastases contained precursor gelatinase A (pMMP2) and precursor gelatinase B (pMMP9), whereas control CSF contained only pMMP2. All patients with positive CSF cytologies had activated MMP2. A similar correlation was observed between the presence of activated MMP9 and positive CSF cytology. CONCLUSIONS: The precursor and activated forms of gelatinases A and B can be detected in the CSF of patients with primary and metastatic brain tumors. The distribution of gelatinase activity in CSF distinguishes patients with malignant gliomas or brain metastases from those without brain tumors, and distinguishes patients with meningeal carcinomatosis from those without CSF spread of tumor, regardless of their brain tumor status. Analysis of MMPs in the CSF may be a sensitive technique for diagnosing CNS tumors and provide an early indication of tumor recurrence. This technique may also provide longitudinal information that would be useful in evaluating ongoing treatment and predicting tumor behavior.

Recurrence of medulloblastoma: violation of Collins' law after two decades.

BACKGROUND: Medulloblastoma is a common tumor of childhood arising in the posterior fossa. The concept of a child with an embryonal tumor surviving the age of diagnosis plus 9 months as the period of risk for recurrence (Collins' Law) has been applied to medulloblastomas. This raises the question of "when should follow-up stop for a patient with this type of tumor?" METHODS: We present a case report of a patient with the longest documented exception to Collins' Law for medulloblastoma. RESULTS: The longest documented exception to Collins' Law, a medulloblastoma recurring 20 years and 8 months after the period of risk for recurrence is presented. Both the site of recurrence and the histopathology were identical to the original tumor. CONCLUSION: We present the longest documented exception to Collins' Law, to emphasize that even after decades the term "cure" should only be used cautiously.

Orbital hematic cyst: case report and clarification of terms.

We present a case of a hematic cyst and review the literature in order to clarify nomenclature discrepancies regarding terms used to describe cysts containing blood and blood breakdown products in and around the orbit. We believe orbital cysts containing blood and blood breakdown products should be separated into two major categories depending on the presence or absence of an epithelial or endothelial lining. A hemorrhage into a preexisting lesion such as a dermoid, on lymphangioma, which contains blood breakdown products lined by an endothelial or epithelial lining, should be referred to as an acute or chronic hematoma in a dermoid or lymphangioma. In contrast, a hematic cyst contains blood breakdown products and has no epithelial or endothelial lining but rather a fibrous pseudocapsule.

A randomized, blinded, placebo-controlled trial of divalproex sodium prophylaxis in adults with newly diagnosed brain tumors.

BACKGROUND: Seizures occur after the diagnosis of brain tumors in up to 40% of patients. Prophylactic anticonvulsants are widely advocated despite a lack of convincing evidence of their efficacy in preventing first seizures. We conducted a randomized, double-blind, placebo-controlled study comparing the incidence of first seizures in divalproex sodium- and placebo-treated patients with newly diagnosed brain tumors. PATIENTS AND METHODS: Patients who had not previously had a seizure were randomized within 14 days of diagnosis of their brain tumor to receive either divalproex sodium or placebo. All patients had at least one supratentorial brain lesion, a Karnofsky Performance Score (KPS) > or = 50%, and no previous anticonvulsant use or other brain disease. Compliance and adequacy of dosing were assessed by pill counts and monthly blood levels. RESULTS: Seventy-four of 75 consecutive eligible patients were entered in this study. Median follow-up was 7 months. The drug and placebo groups did not differ significantly in age, sex, KPS, primary tumor type, number or location of brain lesions, frequency of brain surgery, or pretreatment EEG. Thirteen of 37 patients (35%) receiving divalproex sodium and 9 of 37 patients (24%) on placebo had seizures. The odds ratio for a seizure in the divalproex sodium arm relative to the placebo arm was 1.7 (95% CI 0.6 to 4.6; p = 0.3). The hypothesis that anticonvulsant prophylaxis provides a reduction in the frequency of first seizure as small as 30% was rejected (p = 0.05). CONCLUSIONS: Anticonvulsant prophylaxis with divalproex sodium is not indicated for patients with brain tumors who have not had seizures.

Role of surgery in stage IE non-Hodgkin's lymphoma of the thyroid.

BACKGROUND: Controversy persists regarding the role of surgery in the treatment of stage IE non-Hodgkin's lymphoma of the thyroid. Treatment options vary from complete surgical resection only to needle biopsy as the only invasive procedure required. METHODS: During a 29-year period 15 patients with stage IE non-Hodgkin's lymphoma were treated, with complete follow-up available in all patients. All patients had surgical exploration, followed in most cases by radiation therapy and/or chemotherapy. RESULTS: After operation six patients exhibited no gross residual tumor, all with intrathyroid disease, and all remained disease free; five of nine patients with residual disease, all with extrathyroid lesions, had persistent or recurrent disease (p < 0.04). Among patients with residual disease after operation five of six receiving postoperative radiation therapy exclusively have died of or had recurrence of disease, whereas no further persistent or recurrent disease occurred in the three patients who received adjuvant chemotherapy (p < 0.02). CONCLUSIONS: Surgery permitted the distinction between intrathyroid tumor, which may be treatable by local therapy alone, and extrathyroid lesions, which appear to require systemic chemotherapy. Surgery provides not only the same diagnostic ability as needle biopsy but also important therapeutic implications regarding adjuvant therapy.

The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. I. Assessment of receptive field changes following thalamic reticular nucleus lesions.

1. Changes in the receptive field (RF) properties of thalamic VPM neurons were assessed quantitatively using single-unit recording techniques following a selective excitotoxic lesion of the ipsilateral thalamic reticular nucleus (TRN). The response profiles to controlled deflections of the contralateral vibrissae were obtained from 97 VPM neurons in normal and 102 VPM neurons in TRN-lesioned animals. 2. Histological signs of TRN lesions were detectable in Nissl-stained sections as early as 20 h after the release of kainic acid into TRN. 3. The average RF size of VPM neurons in normal animals was 2.39 +/- 0.18 whiskers (mean +/- SE). Immediately after the lesion of TRN, the average RF size in VPM was enlarged significantly and remained expanded for as long as 1 mo after the destruction of TRN (7.64 +/- 0.47 whiskers, P < 0.001). 4. Subsequent lesions of trigeminal subnucleus interpolaris (SpVi) in TRN-lesioned animals produced a marked reduction in the RF size of VPM neurons. The average VPM RF size for TRN/SpVi lesioned animals was 2.14 +/- 0.64 whiskers. 5. The loss of inhibition from TRN increased the average response probability and magnitude to the center RF whisker by 38 and 34%, respectively. The response probability and magnitude of the surround RF whiskers increased by 64 and 69%, respectively. The average response latencies to the center and surround RF whiskers were significantly longer after the lesion of TRN; subsequent lesions of SpVi in TRN-lesioned cases reduced the average response latencies of VPM neurons to those seen in normal animals. 6. The RF of VPM neurons in both normal and TRN lesioned cases displayed a strong anterior-posterior ("row") preference. Immediately adjacent anterior-posterior whiskers were twice as likely to elicit a response in VPM than immediately adjacent dorsal-ventral whiskers. 7. VPM units were tested for a preferential response to whisker movement in one of four directions (up, down, backward, and forward). The majority of the neurons in both normal and TRN-lesioned cases showed direction-selective responses, mostly in the up direction. Thus gamma-aminobutyric acid (GABA)-mediated inhibition in rat VPM does not appear to be responsible for direction selectivity of VPM neurons. 8. Virtually all neurons in rat VPM after TRN lesions displayed responses that were sustained for the duration of the stimulus (25.5% in normal vs. 88.2% in TRN-lesioned cases). VPM units showing sustained (tonic) responses maintained a high rate of spontaneous activity and, on average, responded to 2-3 times more whiskers than phasically responding units.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons.

1. Changes in the response properties of 106 ventral posterior medial (VPM) units were assessed after iontophoretic blockade of gamma-aminobutyric acid-A or -B (GABAA or GABAB) receptor-mediated inhibition using bicuculline methiodide (BIC) or 2-hydroxy-saclofen (2-OH-S), respectively. 2. The iontophoretic administration of either BIC or 2-OH-S did not alter significantly the average spontaneous firing rate of VPM neurons for current intensities between 40 and 80 nA. The presence of 10 mM 2-OH-S (60 nA) was effective in completely reversing the depressant effects of the selective GABAB receptor agonist, baclofen, on the spontaneous activity of VPM neurons. 3. The effect of BIC on whisker-evoked responses was a preferential enhancement in the responses elicited by the whisker giving rise to the highest probability response (center receptive field whisker or CRF). The effect of 2-OH-S (40-80 nA iontophoretic currents) was to increase the responsiveness of VPM neurons to the stimulation of whiskers in all parts of the receptive field (RF), although its influence was much more pronounced in the peripheral areas of the RF (surround receptive field whisker or SRF). This preferential enhancement of SRF-whisker responses after the blockade of GABAB receptor-mediated inhibition resulted in a 2.3-fold increase in the average RF size of VPM neurons; no statistically significant increases in the size of the RF were seen in the presence of BIC. 4. The primary influence of BIC and, to a lesser degree, 2-OH-S was to prolong the response duration of VPM neurons to CRF whisker stimulation. Under our recording conditions, approximately 25% of VPM neurons in normal animals responded with sustained discharges. In the presence of BIC and 2-OH-S, the percent of VPM units that could be classified as tonically responding increased to 82% and 67%, respectively. 5. The proportion of VPM neurons that was selective to the deflection of whiskers in a particular direction (87%) was not altered in the presence of BIC or 2-OH-S. 6. BIC was effective in antagonizing GABA-mediated inhibition within the first 40 ms of a stimulus; BIC was completely ineffective in reversing a late suppression seen between 80 and 140 ms. In contrast, no statistically significant changes in the initial GABA-mediated inhibition were seen in the presence of 2-OH-S, but 2-OH-S was partially effective in antagonizing the late suppression of responses in VPM neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

The radiographic diagnosis and treatment of paraneoplastic central nervous system disease.

Paraneoplastic nervous system syndromes are being identified with increasing frequency because of greater physician awareness and the availability of serodiagnostic tests for some syndromes. Frequently, paraneoplastic syndromes develop in the setting of an indolent, limited stage, or otherwise occult malignancy. As a result, the paraneoplastic disorder often becomes the most disabling part of a patient's disease. Effective treatment appears to require early identification. For these reasons, the ability to diagnose a paraneoplastic syndrome, follow its course, and treat it successfully are important. The authors describe four patients with neurologic paraneoplastic syndromes and identical magnetic resonance imaging abnormalities. Three patients responded to immunosuppressive or immunomodulatory therapy, and in one, corresponding radiographic improvement was documented. Strategies for early diagnosis and options for treatment of paraneoplastic nervous system disorders are discussed.