Uncrossed Asymmetry in Pattern Visual Evoked Potentials: A Reappraisal.

PURPOSE: To demonstrate the utility of an uncrossed asymmetry in full-field pattern reversal visual evoked potentials (FF-PVEPs) will accurately predict a retrochiasmal lesion confirmed by MRI. METHODS: During an 8-year period, 754 patients had FF-PVEPs performed and analyzed without knowledge of their clinical histories and imaging studies. Interhemispheric amplitude ratios were calculated between N75-P100 and P100-N145 and deemed significant if both demonstrated greater than 50% amplitude asymmetry no matter which eye was stimulated (uncrossed symmetry). RESULTS: We identified 11 patients of 754 patients evaluated for 8 years (1.5%) whose FF-PVEP fulfilled our amplitude criteria. Ten of 11 had retrochiasmal lesions confirmed with MRI for a calculated positive predictive value of 91%. CONCLUSIONS: These data provide initial support for the hypothesis that specified amplitude criteria in FF-PVEPs can provide evidence for a retrochiasmal lesion. An abnormal interhemispheric amplitude ratio in FF-PVEPs is underrecognized as a diagnostic criterion for retrochiasmal lesion prediction.

Aphasic status epilepticus: electroclinical correlation.

PURPOSE: Aphasic status epilepticus (ASE) in otherwise awake patients is a rare phenomenon. We present a series of nine consecutive patients with ASE to characterize clinical, electrophysiologic, and imaging findings. METHODS: Nine patients in ASE were identified between July 2006 and December 2009 at our institution. Each was evaluated by the neurology service and monitored with video-electroencephalography (EEG) for at least 24 h. Thorough, repeated language testing was correlated with EEG findings. KEY FINDINGS: All nine patients were right-handed with subacute or chronic left hemispheric lesions on magnetic resonance imaging (MRI). All patients had mixed aphasia, three presenting with persistent aphasia from onset and six with episodic speech impairment, which became persistent in five of the six. The initial 30-min EEG demonstrated electrographic seizure in only five patients (56%), despite the presence of aphasia during the recording. Left hemispheric periodic lateralized epileptiform discharges (PLEDS) were seen in two patients, and left hemispheric slowing in two patients. Continuous video-EEG monitoring confirmed electrographic seizure activity in all nine patients. Peak electrographic seizure frequency varied from continuous to once every 2 h and was not associated with fluctuations in the speech deficit. EEG seizures resolved abruptly in three patients and gradually over up to 4 days in six patients. Clinical improvement was delayed in eight of the nine patients, and four patients retained some aphasia at discharge, 2-4 days after EEG seizure resolution. SIGNIFICANCE: Standard EEG is sensitive for detection of abnormalities in the dominant hemisphere in patients with ASE. However, continuous EEG is necessary to confirm the diagnosis and monitor treatment, since clinical symptoms do not correlate with electrographic seizure activity and do not provide sufficient information to guide treatment decisions.

Comparative safety and efficacy of topical hemostatic agents in a rat neurosurgical model.

OBJECTIVE: Adequate hemostasis is extremely important in neurosurgery, commonly requiring the use of topical hemostatic agents. Apart from variable efficacy, the residual presence of these agents may cause foreign body reaction, infection, and delayed bone growth. This study compares the safety and efficacy of commonly used agents with a newly approved agent, Arista (microporous polysaccharide hemospheres; Medafor, Inc., Minneapolis, MN). METHODS: A brain tissue defect was created in 228 Wistar outbred rats, and either no agent (negative control), Arista, Surgicel (oxidized cellulose; Ethicon, Inc., Somerville, NJ), Avitene (microfibrillar collagen; Alcon, Inc., Humacao, PR), FloSeal (gelatin matrix thrombin sealant; Baxter Healthcare Corp., Deerfield, IL), or kaolin (positive control) was implanted. Time to hemostasis was documented. The animals were sacrificed at different intervals up to 28 days, and presence of residual material and foreign body reaction was determined. RESULTS: Arista, Avitene, FloSeal, and Surgicel performed better (defined as complete hemostasis within 1 minute) than control (no treatment). Residual material was not present at any time with Arista, markedly contrasting with the presence of residual material in 100% of lesions in the Avitene, FloSeal, and Surgicel groups on Day 14. Avitene and FloSeal also demonstrated a propensity for causing granuloma formation, whereas Arista and Surgicel showed no such evidence. CONCLUSION: Each of these hemostatic agents was effective in controlling bleeding in the majority of standardized neurosurgical lesions. Arista degrades more rapidly than Surgicel, Avitene, and FloSeal and does not result in any foreign body reaction.

Potent nonpeptide vasopressin receptor antagonists based on oxazino- and thiazinobenzodiazepine templates.

Vasopressin receptor antagonists can elicit ion-sparing diuretic effects (i.e., aquaresis) in vivo by blunting the action of the circulating hypophyseal hormone arginine vasopressin. We have identified two new series of basic tricyclic benzodiazepines, represented by general structure 1, which contain compounds that bind with high affinity to human V2 receptors. For example, (S)-(+)-8 and 5 are potent and selective V2 receptor antagonists with pronounced aquaretic activity in rats on oral administration.

2,5-disubstituted 3,4-dihydro-2H-benzo[b][1,4]thiazepines as potent and selective V2 arginine vasopressin receptor antagonists.

A number of 2,5-disubstituted benzothiazepines were synthesized and screened for their ability to inhibit arginine vasopressin binding to the human V(2) and V(1a) receptor subtypes. The more active compounds were subsequently analyzed for their antagonist activity in in vitro functional assays. The SAR showed a preference for an acidic unit appended from the benzothiazepine scaffold. This substitution pattern afforded the most potent and selective analogues in the series. The carboxymethyl analogue 4, showed a 140-fold greater selectivity for the V(2) over the V(1a) receptor in the binding assay. In the cell-based functional assays this analogue was a potent and selective antagonist of the V(2) receptor. The in vitro SAR of the series and a description of the in vivo studies around compound 4 is described.

Synthesis and biological evaluation of novel indoloazepine derivatives as non-peptide vasopressin V2 receptor antagonists.

A series of novel 3,4,5,6-tetrahydro-1H-azepino[4,3,2-cd]indoles was synthesized and tested for vasopressin receptor antagonist activity. We identified compounds with high affinity for the human V2 receptor and good selectivity over the human V1a receptor. Compound 6c bound to V2 receptors with an IC(50) value of 20 nM, had >100-fold selectivity over V1a receptors, and inhibited cAMP formation in a cellular V2 functional assay with an IC(50) value of 70 nM.