Biomedical subjects

M D Privitera

Publications and source records attributed to M D Privitera.

31 records · Page 2Linked to original sources

PubMed1995

Repetition and the arcuate fasciculus.

According to the traditional model of language organization, repetition deficits arise following damage to the arcuate fasciculus of the dominant hemisphere (conduction aphasia). Conduction aphasia may result from lesions that spare the arcuate fasciculus. However, these patients have atypical language organization. We describe a man with normal language architecture who underwent a resection of the anterior portion of his arcuate fasciculus and retained his ability to repeat words and sentences. We propose that the arcuate fasciculus is not necessary for speech repetition by the lexical route.

Adult↗

PubMed1995

Seizure control and extent of mesial temporal resection.

Controversy exists about the extent of mesial temporal lobe resection that improves seizure control in patients with temporal lobe epilepsy. In this retrospective study, 70 patients with mesial temporal seizure activity (without evidence of tumor or vascular malformation) were surgically treated and followed for at least 2 years. The extent of mesial temporal resection was based on the findings of interictal and ictal discharges using depth electrodes, which were inserted preoperatively or intraoperatively by the orthogonal approach to the amygdaloid and hippocampal regions. Only the amygdala was resected along with the limited lateral neocortex if no epileptiform activity involved the hippocampus. The amount of hippocampal excision was determined by the extent of interictal seizure activity. The following groups became seizure free: all 8 patients with only amygdalar resection; 6 of 10 patients with amygdalar and < or = 1 cm hippocampal resection; 23 of 38 with 1-2 cm hippocampal removal, and 11 of 14 with > 2 cm hippocampal excision. In cases where there was no hippocampal resection, neuropsychological outcome compared favorably with controls. Our results suggest that although most patients with temporal lobe epilepsy require hippocampal resection of varying degrees, there is a subset in whom the amygdala may be the crucial element of a mesial temporal epileptogenic network. These patients can undergo a surgical resection sparing the hippocampus without compromising seizure outcome.

Adult↗

PubMed1995

Lesionectomy versus electrophysiologically guided resection for temporal lobe tumors manifesting with complex partial seizures.

Complex partial seizures associated with tumors and other mass lesions are readily diagnosed by modern imaging techniques but their optimum surgical treatment remains unresolved. Lesionectomy has been reported to produce seizure outcomes equal to outcomes after resection that ablates the epileptogenic cortex with the lesion. However, some evidence suggests that when the lesion is in the temporal lobe, simple excision of the tumor or lesion more often fails to control seizures. After retrospectively reviewing the records of 30 patients with complex partial seizures and temporal lobe tumors who underwent surgical treatment at the University of Cincinnati hospitals (1985-1992), the authors divided them into two groups: Group A (16 patients) underwent lesionectomy only and Group B (14 patients) received surgical treatment for seizures with electroencephalographic delineation of the epileptogenic zone and resection of the lesion. Seizure control was best achieved in Group B patients with 13 (92.8%) seizure free at follow up (mean 52 months). Only three (18.8%) of the Group A patients became seizure free after lesionectomy at follow up (mean 33 months). In eight Group A patients, who underwent temporal lobectomy as a second procedure after lesionectomy failed to control seizures, five (62.5%) became seizure free. Group B patients had a longer duration of seizures and were more likely to have lesions smaller than 2.5 cm compared with Group A. Analysis of covariance demonstrated that the differences in outcome between the groups remained significant even with adjustment for the variation in duration of seizures (p = 0.0006) and size of tumor (p = 0.0001). Based on this study, the authors found that the probable relief from seizures caused by a temporal lobe lesion is greater if the region of epileptogenicity, usually the amygdalohippocampal complex, is resected along with the tumor in a temporal lobectomy.

Adolescent↗

PubMed1994

Experimental seizures in the frog (Rana pipiens).

We investigated the effects of chemical convulsants in the leopard frog. Systemic kainic acid (5-20 mg/kg) caused limbic-like seizures, with staring, catatonia, fasciculations, and severe motor seizures, which were almost always lethal. Intracerebral electroencephalographic (EEG) recordings showed spike or spike-and-wave patterns at 6-8 Hz that decreased in frequency and increased in amplitude, maximal at an electrode in the midline olfactory/telencephalic (OLF-M) region. With time, an interictal pattern of 100-200 microV periodic spikes developed, followed by diffuse suppression of all brain activity. Seizures induced by pentylenetetrazole (150-450 mg/kg) and bicuculline (5-10 mg/kg) were characterized by the abrupt onset of motor activity, which continued intermittently for several hours, followed by recovery. EEG recordings in animals treated with pentylenetetrazole showed rhythmic spike-and-wave bursts at 1.5-3 Hz that were maximal at OLF-M. Recordings from frogs treated with bicuculline showed repetitive 3-6 Hz spike-and-wave discharges maximal at OLF-M that were nearly constant in amplitude and at times became continuous. Strychnine (1-5 mg/kg) caused reversible seizures characterized by tonic extensions of the extremities, that seemed to originate in the spinal cord. Frogs with recurrent seizures from systemic cis-diamminedichloroplatinum II showed 4-8 Hz rhythmic spike-and-wave activity that gradually slowed in frequency and increased in amplitude. Thus, the frog's reactivity to convulsive agents is similar to that of mammals.

Animals↗

PubMed1994

Dezinamide for partial seizures: results of an n-of-1 design trial.

BACKGROUND: Dezinamide (DZM, ADD 94057) is a potential antiepileptic drug that binds to the voltage-sensitive sodium channel and showed preliminary evidence of efficacy and safety in an open-label study. METHODS: Our double-blind, placebo-controlled trial at two sites used an n-of-1 (single-patient) design. All 15 patients had medically intractable partial-onset seizures and were comedicated with phenytoin (PHT) only. Treatment was for six 5-week periods (three active paired with three placebo in random sequence). Assuming nonlinear kinetics, we used an initial pharmacokinetic profile to estimate dosages for reaching target plasma concentrations of DZM. RESULTS: Statistically significant seizure reduction was found by both a randomization test (p = 0.0025) and a signed rank test (p = 0.048). Median seizure frequency decreased 37.9%, and 40% of patients had > 50% seizure reduction, both compared with placebo. Pharmacokinetic predictions were not accurate; mean plasma concentrations fell well below target values. Plasma PHT concentrations increased (mean = 17.1%) during DZM treatment. The most common adverse experiences were fatigue, light-headedness, and abnormal gait; five patients required DZM dosage reductions. CONCLUSIONS: DZM showed minimal clinical toxicity and significant efficacy despite lower plasma concentrations than predicted by pharmacokinetics. This trial establishes the suitability of the n-of-1 design to investigational antiepileptic drug trials.

Adult↗

PubMed1994

Electroencephalographic monitoring in the emergency department.

EEG is the single most important test in diagnosing epilepsy and related conditions. We urge immediate EEG for patients with persistent, unexplained, altered consciousness. In our prospective study, 37% of patients referred for emergency EEG had combined EEG and clinical evidence of SE that was not tonic-clonic that would have gone undetected without EEG. In some cases, EEG provides useful diagnostic information or clarifies the severity of brain dysfunction in comatose patients. Finally, EEG is essential in monitoring patients who require pentobarbital coma for refractory SE.

Adult↗

PubMed1993

Clinical rules for phenytoin dosing.

OBJECTIVE: To develop simple clinical rules for dosing phenytoin (PHT) using computer simulations, then to test the rules for accuracy and safety on actual patient data. DESIGN: Patients with steady-state PHT plasma concentrations at least two different PHT doses were identified from three separate sources of patient data. A computerized dosing program calculated pharmacokinetic parameters using Bayesian methodology, then predicted how many patients were likely to reach potentially toxic PHT plasma concentrations when their daily dosage was increased by 30, 50, or 100 mg. Dosing rules were developed to allow fewer than ten percent of resultant plasma concentrations to exceed 25 micrograms/mL. The dosing rules then were tested on dose/plasma concentration data from a separate group of patients. SETTING: All patients were being treated by neurologists either as outpatients or inpatients. PATIENTS: All patients were adults with epilepsy being treated with PHT; none had clinically significant renal or hepatic disease. Patients for the computer simulation were from three sources: (1) patients who had an initial PHT plasma concentration < 10 micrograms/mL and required a dosage increase; (2) patients admitted to the hospital for PHT intoxication; and (3) patients who required consultations specifically for PHT dosing. Patients on whom the dosing rules were tested were part of a prospective, randomized trial of antiepileptic drug safety and efficacy. MAIN OUTCOME MEASURES: Successful dosing rules allowing fewer than ten percent of resulting plasma concentrations in the test group to exceed 25 micrograms/mL. RESULTS: The simulations used 167 actual dose/plasma concentration pairs from 45 patients. The resulting dosing rules were: increase the dosage by 100 mg/d if the initial plasma concentration was < 7 micrograms/mL; increase the dosage by 50 mg/d if the initial plasma concentration is 7 to < 12 micrograms/mL; increase the dosage by 30 mg/d if the initial plasma concentration is > or = 12 micrograms/mL. The rules were tested on 129 50- or 100-mg dosage increases in 77 patients. All 53 dosage increases that were within the dosing rules produced plasma concentrations < 25 micrograms/mL, whereas 36 percent (27 of 74) of the dosage increases that exceeded the dosing rules produced plasma concentrations > 25 micrograms/mL. CONCLUSIONS: The proposed dosing rules are a simple method for clinicians to estimate PHT dosage changes and appear to be safe and accurate when applied retrospectively to actual patient data.

Adult↗

PubMed1991

Secondary epileptogenesis in cerebral arteriovenous malformations.

There is debate as to whether secondary epileptogenesis occurs in humans. As part of a series of patients with cerebral arteriovenous malformations and epilepsy, we identified two patients with probable secondary epileptogenesis in the mesiotemporal regions, ipsilateral but anatomically distant from an arteriovenous malformation causing seizures. Both patients had arteriovenous malformations outside the mesiotemporal region and resection of the arteriovenous malformation and epileptogenic areas identified by electrocorticography produced initial freedom from seizures. Three to 6 months later both patients developed a different seizure pattern that proved to be mesiotemporal in origin by video/electroencephalogram (one with depth electrodes) and both patients are seizure free after a second resection of anterotemporal and mesiotemporal regions. Findings indicating a secondary epileptogenic focus include (1) different seizure type by patient history, (2) second seizure type by ictal video/electroencephalographic recordings, and (3) lack of pathologic abnormalities in the resected mesiotemporal specimens.

Adult↗

PubMed1991

Postictal language assessment and lateralization of complex partial seizures.

We performed a prospective study of ictal and postictal language function after 105 temporal lobe complex partial seizures in 26 patients. Seizure localization was verified by a greater than 90% reduction in seizure frequency after temporal lobectomy. At the time of the seizure, the patient was asked to read a test phrase aloud until it was read correctly and clearly. In all 62 seizures originating from the left temporal lobe, the patient took more than 68 seconds to read the test phrase correctly (mean, 321.9 seconds); in 42 of 43 seizures from the right temporal lobe, the patient read the test phrase in less than 54 seconds (mean, 19.7 seconds). Postictal paraphasias occurred in 46 of 62 seizures from the left temporal lobe (11 of 14 patients). In this study, quantifying the time delay in reading a test phrase lateralized seizure onset in all 26 patients tested, proving significantly more accurate than any other single noninvasive presurgical test.

Adolescent↗

PubMed1990

Interictal spike detection comparing subdural and depth electrodes during electrocorticography.

We compared the ability of subdural and depth electrodes to detect and localize interictal epileptiform discharges (IEDs) in the temporal lobe. Sixteen patients had simultaneous intraoperative recordings with depth and subdural electrodes while undergoing anterior temporal lobe resections under local anesthesia for medically intractable seizures. IEDs that were focal (detected at just 1 or 2 electrode contacts) typically registered at the nearest contact, regardless of type. IEDs that were regional (engaging more than 2 electrode contacts) typically appeared simultaneously at both electrode types. Neither method was better able to indicate whether an IED was mesial or lateral, posterior or anterior. Subdural and depth electrodes seem to provide complementary information on the location of IEDs within the temporal lobe.

Electrodes, Implanted↗

PubMed1989

Clinical utility of a Bayesian dosing program for phenytoin.

We performed two studies to assess the clinical utility of a Bayesian regression analysis computer program for phenytoin (PHT). In a randomized prospective study of 40 epileptic patients, the dosing program was significantly more accurate (p = 0.002) and less biased (p = 0.02) than a group of physicians at hitting a target PHT serum-concentration. Initial serum PHT concentrations that were not steady state were associated with the largest dosing errors by physicians but did not affect the accuracy of the dosing program. In a second study, we used the dosing program to predict 91 serum concentrations in 31 patients with PHT toxicity after the drug was stopped (initial concentration 26-69 micrograms/ml). The program predicted serum concentrations with a mean error of 3.49 +/- 0.29 micrograms/ml without significant tendency to over- or underpredict. We conclude that this dosing program may aid clinicians by improving dosing accuracy and predicting serum concentrations in patients with PHT toxicity.

Adolescent↗

PubMed1989

Dosing accuracy of antiepileptic drug regimens as determined by serum concentrations in outpatient epilepsy clinic patients.

To evaluate the ability of clinicians to accurately dose antiepileptic drugs (AEDs), 2,958 serum concentrations in two outpatient epilepsy clinics were studied. Serum concentrations of phenytoin (PHT) were significantly less likely to fall within the therapeutic range (TR) when compared to carbamazepine (CBZ) or phenobarbital (p less than 0.0001) even when there was evidence that patient compliance was good. This difference remained significant when the second through fourth follow-up serum concentrations were analyzed. PHT concentrations were more likely to be below than above the TR (p less than 0.0001). CBZ concentrations were least likely of the three AEDs to be below the TR (p less than 0.01). Analysis of factors influencing AED metabolism and of data from previous studies implies that saturable metabolism and variable time to steady state for PHT are responsible for these findings. These results support the increased use of dosing aids for PHT that may help clinicians more accurately choose PHT doses and estimate time to steady state.

Anticonvulsants↗

PubMedDate not supplied

Psychopathology and trauma in epileptic and psychogenic seizure patients.

Forty-one patients admitted to an inpatient epilepsy unit for intractable seizures were evaluated for the presence of Axis I and Axis II diagnoses and for a history of trauma by use of a structured clinical interview. Both the interviewer and the patient were blind to the seizure diagnosis. Following video and electroencephalographic evaluation, 27 patients were diagnosed with epileptic seizures, and 14 had psychogenic seizures. The history of Axis I and Axis II disorders did not distinguish the two groups of patients. A history of trauma was significantly more likely in the patients with psychogenic seizures. The experience of trauma appears to be an important factor in the development of psychogenic seizures. Sexual trauma alone, however, was not significantly associated with psychogenic seizures.

Adolescent↗