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Biomedical subjects

M Privitera

Publications and source records attributed to M Privitera.

At least 19 recordsLinked to original sources
PubMed1998

Increased seizure frequency associated with felbamate withdrawal in adults.

OBJECTIVE: To characterize changes in seizure frequency following felbamate withdrawal. DESIGN: Nonrandomized, retrospective chart review of a case series. SETTING: Epilepsy program specializing in adults with uncontrolled epilepsy. PATIENT POPULATION: Forty-five ambulatory patients withdrawn from felbamate use. Patients were included if they had received felbamate for at least 1 month, were 18 years or older, had accurate seizure frequency documentation, had accurate documentation of all antiepileptic drugs, and received the same concomitant antiepileptic drugs before and after felbamate therapy, except for the possible addition of gabapentin. Patients were excluded if they had hematologic or hepatic toxic effects with felbamate, were unable to withdraw from felbamate treatment, had a progressive neurologic disorder, or participated in another drug trial. METHODS: When information became available on aplastic anemia and hepatotoxicity associated with felbamate, all patients were advised to taper their felbamate dosage over approximately 2 weeks. They received written instructions for tapering felbamate and adjusting concomitant antiepileptic drugs and kept calendars to note the number of seizures. The charts of all patients who received felbamate were evaluated for adherence to inclusion and exclusion criteria. Statistical analysis was performed using a log-linear model for count data. MAIN OUTCOME MEASURES: Seizure frequency during the 6 months before initiating felbamate therapy served as the baseline. Changes in seizure frequency were evaluated by comparing the number of seizures in the month felbamate was tapered and the 3 months after felbamate discontinuation with the baseline frequency. Comparisons were made between patients who started gabapentin therapy and those who did not and between felbamate responders and nonresponders. RESULTS: Felbamate withdrawal resulted in a significant (P=.02) increase in seizure frequency. Patients receiving gabapentin had a smaller increase in seizure frequency, but the difference was not statistically significant. There was no statistically significant difference in seizure frequency between felbamate responders and nonresponders. CONCLUSIONS: Felbamate withdrawal caused a significant increase in seizure frequency over the subsequent 3 months. These findings are important for clinical trial design and clinical practice.

Acetates↗
PubMed1998

Standards of laboratory practice: antiepileptic drug monitoring. National Academy of Clinical Biochemistry.

Discussion and development of standards for appropriate monitoring led to the following key recommendations for ordering, sampling, and analyzing antiepileptic drugs: Monitoring should usually be done on trough specimens after steady-state has been reached and always with an appropriate medical indication; non-steady-state concentrations may be indicated in selected situations. Monitoring of free phenytoin and free valproic acid is indicated in specific situations and should be done in serum. The metabolite of primidone, phenobarbital, should be measured concurrently with parent drug, but the active metabolite of carbamazepine does not need to be monitored unless the patient is exhibiting an unusual toxic response that cannot be otherwise explained. Assays used for antiepileptic drug monitoring should display a long-term CV of <10% and preferably <5%. Subtherapeutic and supratherapeutic drug concentrations should be investigated on a regular basis as part of a quality assurance process.

Anticonvulsants↗
PubMed1997

Long-term experience with topiramate as adjunctive therapy and as monotherapy in patients with partial onset seizures: retrospective survey of open-label treatment.

Because initial studies of new antiepileptic drugs (AEDs) are add-on trials in refractory patient populations, their effectiveness as monotherapy is usually not apparent until relatively later in their development programs. The novel AED topiramate (TPM) has been found efficacious as adjunctive therapy in controlled, randomized trials in adults with partial onset seizures. We report a retrospective analysis of TPM as AED monotherapy in 214 patients from five centers who received TPM in investigational trials. Of this total, 136 (64%) were still receiving TPM at the time of the analysis, with a mean treatment duration of 2.5 years. One-third of the patients have been successfully converted to TPM monotherapy, and 62% of those converted have been seizure-free for at least 3 months. The results of this analysis suggest that TPM may prove to be a valuable new AED for both monotherapy and add-on therapy in partial onset epilepsy.

Adult↗
PubMed1996

Acute phenytoin toxicity followed by seizure breakthrough from a ticlopidine-phenytoin interaction.

OBJECTIVE: To review a case of a drug-drug interaction between phenytoin sodium and ticlopidine hydrochloride that resulted in acute phenytoin toxicity and permanent memory loss. CASE REPORT: A 63-year-old man who was maintained with a stable dose of phenytoin for treatment of seizures began treatment with ticlopidine following percutaneous transluminal angioplasty and stent placement. Within 3 weeks of beginning treatment with ticlopidine, he experienced acute clinical toxic effects of phenytoin with a maximum measured phenytoin concentration of 162.4 micromol/L. Phenytoin concentration decreased to 36 micromol/L after discontinuing treatment with ticlopidine and reducing the phenytoin dose. Subsequently, the patient developed probable complex partial status epilepticus. CONCLUSIONS: Ticlopidine is a metabolic inhibitor of several drugs. Because of the potential for acute and permanent adverse effects from a drug-drug interaction, phenytoin concentrations should be carefully monitored when beginning or ending ticlopidine therapy.

Drug Interactions↗
PubMed1996

Postictal language dysfunction in patients with right or bilateral hemispheric language localization.

PURPOSE: As shown previously, when temporal lobe complex partial seizures (TLCPS) originate from the language dominant hemisphere, patients cannot read a test phrase correctly within 60 s of the end of the ictal discharge. We wished to assess whether postictal language testing results discordant with this pattern identified patients with non-left (right hemisphere or mixed) language dominance. METHODS: Since 1988, all patients undergoing video/EEG monitoring at our institution have been given a test phrase to read aloud as soon as a seizure is detected. Inclusion criteria for this study were (a) postictal language testing within 60 s of seizure end for at least one TLCPS, (b) > 90% seizure reduction after anterior temporal lobectomy with 2-year minimum follow-up, and (c) language localization by either intracarotid amobarbital test (IAT) or direct electrical stimulation of left hemisphere cortex. RESULTS: Two hundred twenty-four seizures in 64 patients were analyzed. Discordant postictal language patterns were noted in 10 of 11 patients with IAT documented non-left language dominance and in 15 of 53 with left dominance (p = 0.006; sensitivity 90.9%, specificity 71.7%). CONCLUSIONS: Postictal language testing accurately identifies patients with non-left language dominance and may be useful in selecting appropriate patients for IAT.

Adult↗
PubMed1996

Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 600-, 800-, and 1,000-mg daily dosages. Topiramate YE Study Group.

We conducted a multicenter, double-blind, randomized, parallel, placebo-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunctive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41% for topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. There was a 50% or greater reduction from baseline in seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day, 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 100% in seizure frequency, whereas 20% of the topiramate patients were improved to this degree. All intent-to-treat drug-placebo comparisons including seizure reduction, percent responders, and investigator and patient global evaluations significantly (p < or = 0.02) favored topiramate. Treatment-emergent adverse events consisted mainly of neurologic symptoms commonly observed during antiepileptic drug (AED) therapy. Sixteen percent of patients on topiramate discontinued therapy due to adverse events. Results of this study indicate that topiramate is a highly efficacious and generally well tolerated new AED. When large groups of patients are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher doses may prove beneficial to individual patients who tolerate them.

Adolescent↗
PubMed1994

EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness.

Subtypes of status epilepticus (SE) without tonic-clonic convulsions (nontonic-clonic SE) present as altered consciousness sometimes with subtle motor activity and are important to consider in the differential diagnosis of patients with unexplained altered consciousness. Other patients may have altered consciousness with intermittent ictal activity on electroencephalography (EEG) that represents probable SE, but have other medical conditions that may be contributing to altered consciousness. EEG is the only reliable way to make the diagnosis of nontonic-clonic SE and we make emergency EEG available on a 24-h basis at our hospital. To determine how often definite or probable nontonic-clonic SE was detected by EEG we prospectively collected data on all cases where physicians ordered EEG to evaluate altered consciousness or possible SE. Out of 198 cases with altered consciousness but no clinical convulsions, 74 (37%) showed EEG and clinical evidence of definite or probable nontonic-clonic SE. Forty-two episodes (57%) were probable or definite complex partial SE, 29 (39%) were probable or definite subtle generalized SE, and three (4%) were myoclonic SE. In 23 SE cases altered consciousness was the only clinical sign at the time of diagnosis; subtle motor activity was present in 36 others. Neither clinical signs nor prior history predicted which patients showed SE on EEG. Nontonic-clonic SE followed a cerebral infarction in 16 cases. Contrary to other reports, we found no relationship between duration of SE and EEG pattern. Subtle generalized SE occurred most commonly in the setting of a diffuse brain injury rather than evolving from convulsive SE. This study demonstrates that nontonic-clonic SE is a common finding in patients with unexplained altered consciousness and EEG is necessary in the evaluation of these patients.

Adolescent↗
PubMed1994

Is erythropoietin-induced hypertension a phenomenon due to the intracellular Ca++ mobilisation?

UNLABELLED: The authors evaluated the ability of rHuEPO (recombinant human erythropoietin) in performing a vasoactive calcium-mediated action. Forty healthy volunteers were evaluated for the muscle blood flow at rest (RBF) and after reactive hyperemia by Xenon 133 clearance. Pre-treatments with several calcium antagonists were used. RESULTS: The i.v. infusion of rHuEPO brought about a reduction of the RBF and MBF (maximal blood flow). This reduction was maintained with nifedipine or verapamil. Gallopamil and ketanserine prevented the reduction of blood flow induced by rHuEPO. CONCLUSIONS. The rHuEPO has a vasoconstrictive action in vivo since gallopamil and ketanserine, drugs able to prevent intracellular mobilisation of the Ca++, can block the rHuEPO induced vasoconstriction. The action exerted by rHuEPO could be due not an increased flow of the Ca++ from the extracellular department but to a mobilisation from Ca++ deposits.

Adult↗
PubMed1991

Differences in superficial and deep source contributions to middle latency auditory evoked potential Pa component in normal subjects and patients with neurologic disease.

Multichannel brain-mapped middle latency auditory evoked potential (MLAEP) data obtained from 15 normal subjects and three neurologically impaired subjects using the common average reference (CAR) were converted off-line to source current density (SCD). This technique is sensitive to activity generated in the superficial cerebral cortex. The SCD maps were subtracted from the CAR maps (CAR-SD). The derived CAR-SD maps are believed to represent the proportion of scalp-recorded activity that is generated deep to the cerebral cortex. Topographic analysis of this data manipulation technique supports the hypothesis that Pa originated from within the temporal lobes bilaterally as well as from a deeper subcortical system.

Adult↗
PubMed1990

The effects of anterior temporal lobectomy (ATL) on the middle-latency auditory evoked potential (MLAEP).

The anatomical and physiological origins of the middle-latency auditory evoked potential (MLAEP) are not well understood. The present investigation was conducted to determine whether the MLAEP derives its origins in part from the anterior temporal lobe. Twelve subjects with intractable seizures were evaluated with the MLAEP pre and post excision of the anterior-mesial temporal lobe (ATL) unilaterally. In our study, component Pa latency was unaffected by the ATL. The Na latency and the Na/Pa amplitude showed significant increases after ATL. The results we interpreted as being consistent with currently held beliefs regarding the origins of Pa. The changes in Na latency and Na/Pa amplitude are hypothesized to reflect a loss of the modulating influence of the cortex on the subcortical generators of Na.

Adult↗
PubMed1990

Pericyte degeneration and thickening of basement membranes of cerebral microvessels in complex partial seizures: electron microscopic study of surgically removed tissue.

Complex partial seizures are associated with alterations in regional cerebral blood flow in abnormally spiking foci, as shown by positron emission tomography and single photon emission computed tomography, with an increase in flow ictally and a decrease interictally. Alterations of vasoregulation during ictal periods have also been described in animal seizure models. An electron microscopic study on human brain tissue from seven patients undergoing resections for the treatment of intractable complex partial seizures was performed to examine ultrastructural changes of the microvasculature and their locations within the microvessel wall. Biopsies were obtained intraoperatively from temporal lobe regions with electrocorticographically detected abnormal spiking and from regions without abnormality on electrocorticograms (control samples) removed as part of the therapeutic resection. A total of 539 microvessels from three regions were evaluated: spiking mesial temporal lobe, spiking lateral temporal cortex, and nonspiking (control) cortex. Evidence of pericyte degeneration (aggregates of cellular debris within the basement membrane) was noted in the majority of spiking area microvessels (76.7% in spiking mesial temporal cortex; 69.8% in spiking lateral temporal cortex) as compared with 37.8% of control microvessels (P less than 0.0005). Morphometric studies revealed a significant increase in total wall thickness, pericyte-basement membrane unit thickness, pericyte cytoplasmic density, basement membrane density, and basement membrane thickness in microvessels from spiking (mesial and lateral temporal cortex), as compared to control areas (P less than 0.01). No statistically significant difference was noted in pericyte coverage or pericyte or endothelial mitochondrial densities between microvessels in spiking and control regions. This study shows degeneration of pericytes, cells thought to play an essential role in microvascular hemodynamics, and thickening of microvessel walls in abnormally spiking brain regions in patients with intractable complex partial seizures. The pericyte degeneration and basement membrane thickening in abnormally spiking areas may explain alterations in vasoregulation, by a decrease in the microvascular compliance and in cross-capillary diffusion.

Adult↗