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Biomedical subjects

A Beydoun

Publications and source records attributed to A Beydoun.

At least 19 recordsLinked to original sources

Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400 mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes and, consequently, has a low propensity to inhibit or induce oxidative enzymes and a minimal potential for drug-drug interactions. The efficacy of OXC as monotherapy was shown in several comparative trials in patients with newly diagnosed epilepsy and in hospitalized patients undergoing evaluation for epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel-group trial design was chosen to assess the antiepileptic efficacy of OXC as monotherapy in a refractory epilepsy patient population. Outpatients aged 12 years or older with inadequately controlled partial seizures, with or without secondarily generalized seizures, were enrolled. Patients finished the trial by completing the double-blind phase or by meeting one of four predefined exit criteria: a twofold increase in partial seizure frequency in any 28-day period relative to baseline; a twofold increase in the highest consecutive 2-day partial seizure frequency relative to baseline; occurrence of a single generalized seizure if none occurred during the 6 months prior to randomization; or prolongation or worsening of generalized seizure duration or frequency requiring intervention. Adverse events (AEs), vital signs, and clinical laboratory tests were evaluated. RESULTS: The percentage of patients meeting one of the exit criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a significant difference in time to exit in favor of the OXC 2400 mg/day group (p = 0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day group were seizure-free compared with none in the 300 mg/day group. OXC was well-tolerated, with dizziness, fatigue, somnolence, and nausea being the most frequent AEs. Most of these AEs were transient and rated as mild to moderate in intensity. CONCLUSION: OXC is safe and effective in the treatment of patients with partial epilepsy previously receiving treatment with other antiepileptic drugs. The results of this trial are consistent with previous monotherapy trials with OXC.

Adolescent↗

Safety and efficacy of oxcarbazepine: results of randomized, double-blind trials.

Oxcarbazepine is approved as monotherapy and adjunctive therapy for partial seizures with and without secondarily generalized seizures in adults and as adjunctive therapy for partial-onset seizures in children aged 4-16 years. The clinical development of oxcarbazepine is different from the newer antiepileptic drugs (AEDs) in the extent and concordance of results across clinical trials. The safety and efficacy of oxcarbazepine was evaluated in adjunctive therapy trials, in comparative monotherapy trials with classic AEDs in adults and children with newly diagnosed epilepsy, in monotherapy therapeutic failure design trials in patients with refractory partial seizures, and in trigeminal neuralgia and affective disorder. The results of oxcarbazepine in treating epilepsy are discussed.

Anticonvulsants↗

Measuring the coherence of intracranial electroencephalograms.

OBJECTIVE: Previous coherence studies of human intracranial electroencephalograms (EEGs) can be faulted on two methodological issues: (1) coherence estimates in a majority were formed from a very small number of independent sample spectra, and (2) the statistical significance of coherence estimates was either not reported or was poorly evaluated. Coherence estimator performance may be poor when a small number of independent sample spectra are employed, and the coupling of poor estimation and statistical testing can result in inaccuracy in the measurement of coherence. The performance characteristics of the coherence estimator and statistical testing of coherence estimates are described in this manuscript. METHODS: The bias, variance, probability density functions, and confidence intervals of the estimate of magnitude squared coherence (MSC); and power analysis for the test of zero MSC were developed from the exact analytic form of the probability density function of the estimate of MSC for Gaussian random processes. The coherence of a single epoch of background EEG, recorded from a patient with intractable seizures, was evaluated with different parameter values to aid in the exposition of the concepts developed here. RESULTS: The statistical characteristics of WOSA coherence estimates are a function of a single estimator parameter, the number of independent sample spectra employed in the estimation. Bias and variance are high, confidence intervals may be large, and the probability of Type II errors is high if a small number of independent sample spectra are employed. A considerable improvement in measurement accuracy is possible with careful selection of estimator parameter values. CONCLUSIONS: Coherence measurement accuracy can be improved over previous applications by attention to estimator performance and accurate statistical testing of coherence estimates.

Adult↗

Value of inpatient diagnostic CCTV-EEG monitoring in the elderly.

PURPOSE: To examine the outcome of inpatient diagnostic closed circuit TV-EEG (CCTV-EEG) monitoring in a consecutive series of elderly patients admitted to an adult epilepsy-monitoring unit (EMU) over a continuous 6-year period. METHODS: Retrospective review of all admissions to a university hospital adult EMU. Those older than 60 years were identified. Patients who were monitored for status epilepticus were excluded. Data on duration of events, frequency of events, physical examination, medications, preadmission EEG, brain imaging, length of stay, and interictal and ictal EEG were obtained. RESULTS: Of the 18 patients admitted for monitoring only, mean age was 69.5 years (range, 60-90 years). Mean length of stay was 4.3 days (range, 2-9 days). Five patients had complex partial seizures recorded. Three patients, all treated with anti-epileptic drugs (AEDs), had no spells recorded, and no additional diagnostic information was gained from the admission. The other 10 patients, eight of whom had been treated with AEDs, were symptomatic during their admission, leading to a variety of neurologic but not epileptic, psychiatric, or other medical disorders, and allowing tapering of AEDs. CONCLUSIONS: In elderly patients with suspected epilepsy, CCTV-EEG is a very useful diagnostic tool. In this series of 18, 10 patients were diagnosed with potentially treatable medical illnesses not responsive to AEDs.

Adult↗

Monotherapy trials with gabapentin for partial epilepsy.

The efficacy and safety of gabapentin as monotherapy for treatment of partial onset seizures were evaluated in three large multicenter, double-blind, parallel-group, dose-controlled trials. In the first trial, 275 outpatients with refractory partial epilepsy maintained on stable doses of one or two antiepileptic drugs (AEDs) were switched to gabapentin (GBP) monotherapy at 600 mg, 1200 mg, or 2400 mg daily. Patients were required to exit the 26-week double-blind phase of the study if they experienced worsening of seizure frequency. With respect to time to exit, there was no statistically significant difference among the three groups; only 3% of patients withdrew from the trial because of adverse events. In the second study, 82 hospitalized patients with medically refractory epilepsy were tapered off baseline AEDs and randomly assigned to GBP monotherapy at 300 mg/day or 3600 mg/day. Patients remained in the trial for a maximum of 8 days but had to exit the trial if they experienced one or more exit events. Time to exit was significantly longer in patients in the 3600-mg group (151 h) compared with those in the 300-mg group (85 h) (p = 0.0001). None of the patients withdrew from the trial because of side effects. In the third study, 292 patients with newly diagnosed partial seizures were randomized to GBP 300, 900, or 1800 mg/day or to carbamazepine (CBZ) 600 mg/day. Patients remained in the trial for up to 6 months or until they experienced an exit event. Mean time to exit was significantly longer for patients who received GBP 900 mg/day (p = 0.02) or 1800 mg/day (p = 0.04) compared with those who received 300 mg/day. The completion rate for the CBZ group (37%) was similar to that of the GBP 900-mg (39%) and 1800-mg (38%) groups. Patients receiving CBZ had a higher withdrawal rate because of adverse events compared with the GBP 900-mg and 1800-mg groups. The results of these trials provide good evidence of the efficacy and safety of GBP as monotherapy for the treatment of partial-onset seizures.

Acetates↗

Postherpetic neuralgia: role of gabapentin and other treatment modalities.

Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. The condition occurs in an estimated 50% of patients older than 50 years. The pain of PHN can be severe and debilitating and is frequently associated with allodynia. Although in most patients pain remits within the first year, it may persist for a lifetime. Tricyclic antidepressants (TCAs), topical agents, opioids, and gabapentin, a structural gamma-amino butyric acid (GABA) analogue, are the only agents that have demonstrated efficacy in randomized clinical trials for treatment of both the shooting and the burning form of pain associated with PHN. TCAs are among the most commonly used classes of agents for treating PHN and are effective in a significant proportion of patients. However, various adverse events can limit treatment. These side effects tend to be more acute in the elderly, the population most likely to suffer from PHN. Topical agents have led to mild to moderate improvement in patients with PHN but are usually ineffective as monotherapy for this condition. Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.

Acetates↗

Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial.

CONTEXT: Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies. OBJECTIVE: To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy. DESIGN: Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. SETTING: Outpatient clinics at 20 sites. PATIENTS: The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale. INTERVENTION: Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. MAIN OUTCOME MEASURES: The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results. RESULTS: Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06). CONCLUSION: Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.

Acetates↗

Interictal epileptiform activity in elderly patients with epilepsy.

OBJECTIVE: To examine the frequency of interictal epileptiform activity (IEA) in elderly patients with epilepsy. DESIGN AND METHODS: From a consecutive 13,905 EEGs recorded over 5 years at a university hospital EEG laboratory, 558 studies were performed on outpatients aged 60 years or more. Medical record review identified 125 patients in whom a confident clinical diagnosis of epilepsy was made by a board-certified neurologist. The EEG findings in these patients were reviewed. The effects of various variables on the likelihood of detecting IEA were calculated using Fisher's test and chi-square analysis. RESULTS: IEA were present on the first EEG in 35% of 55 patients (mean age 65 years) with pre-existing epilepsy, and 26% of 70 patients (mean age 70 years) with seizure onset after 60 years. There were no significant differences in the frequency of IEA in patients with late onset epilepsy in the 7th or in the 8th decades of life. Most IEA were focal. Activation procedures added little additional information. Patients with more than one seizure per month were significantly more likely to have IEA (P = 0.016). There were no major differences in likelihood of IEA detection depending on the underlying cause of the seizures. CONCLUSIONS: The frequency of IEA in elderly patients with epilepsy is substantially lower than that reported in epileptic populations as a whole. This low rate of IEA in routine EEG studies must be recognized when considering the diagnosis of an epileptic syndrome for episodic events happening in the elderly.

Aged↗

Responses to photic stimulation in patients with occipital spikes.

OBJECTIVE: To determine the effect of intermittent photic stimulation (IPS) and frequency of asymmetric driving responses in patients with occipital spikes. METHODS: The amplitude of the driving response at 4 flash frequencies was measured from a referential montage in 60 patients with occipital spikes and in 60 normal EEG records from age-matched patients. Responses were classified as asymmetric if the amplitude at one occipital area was less than 50% of the amplitude at the other. RESULTS: A measurable photic response occurred significantly less frequently in patients with occipital spikes (48%) compared to the control group (70%; Fisher's test P < 0.05). The driving response was asymmetric in 7/36 patients (37%) with unilateral spike foci versus none in the control group (Fisher's test, P < 0.001). The amplitude was suppressed ipsilateral to the focus in 5 patients, all of whom had an ipsilateral structural lesion or focal slowing. In two cases the amplitude was higher ipsilateral to the focus, neither having slowing or a structural lesion. CONCLUSIONS: Patients with occipital spikes have an increased frequency of asymmetric driving response. An attenuated response ipsilateral to the focus seems to be related to an underlying lesion while the presence of an epileptiform focus in some cases with no slowing on EEG and normal imaging studies may lead to an accentuation of this response.

Adolescent↗

Conversion to high dose gabapentin monotherapy in patients with medically refractory partial epilepsy.

PURPOSE: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,000-4,800 mg/day) in patients with medically refractory partial epilepsy. METHODS: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed. RESULTS: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,400-4,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related. CONCLUSIONS: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy.

Acetates↗

Collet-Sicard syndrome mimicking neuralgic amyotrophy.

A man with shoulder pain, wasting, and weakness had ipsilateral cranial nerve abnormalities. Electrodiagnostic studies supported a diagnosis of neuralgic amyotrophy, but we later demonstrated a spinal accessory mononeuropathy with ipsilateral hypoglossal weakness (Collet-Sicard syndrome). Magnetic resonance imaging demonstrated an inaccessible occipital condyle mass, and disseminated adenocarcinoma was subsequently diagnosed. Although cranial mononeuropathies can occur in neuralgic amyotrophy, this case illustrates the importance of identifying a focal lesion, and highlights the localizing value of electrodiagnosis.

Aged↗

Human intramuscular and cutaneous pain: psychophysical comparisons.

We used psychophysical methods to compare the central processing of nociceptive inputs from skin and muscle in ten normal humans. Both intramuscular electrical and infrared CO2 laser cutaneous stimulation showed increasing but decelerating (downward concave) stimulus-response curves and similar temporal summation characteristics. Intramuscular stimulation was rated significantly more unpleasant than cutaneous stimulation. The results are consistent with a common mode of central nociceptive processing for skin and muscle pain intensity but suggest a relatively larger activation of affective mechanisms by muscle afferents.

Adult↗

Mutual information analysis and detection of interictal morphological differences in interictal epileptiform discharges of patients with partial epilepsies.

The purpose of this paper is to compare the morphological features of interictal epileptiform discharges (IED) in patients with benign epilepsy of childhood with centrotemporal spikes to IED of those with symptomatic localization related epilepsies using information theory. Three patients from each clinical group were selected. Two-second epochs centered at the peak negativity of the sharp waves were analyzed from a referential montage during stage I sleep. The epochs from the two groups were compared using parametric and information theory analysis. Information analysis determined the likelihood of correctly identifying the clinical group based on the IED. Standard parametric, morphological and spectral analyses were also performed. We found no significant difference in the morphology of the sharp wave between the two groups. The after-going slow wave contained the greatest information that separated the two groups. This result was supported by morphological and spectral differences in the after-going slow wave. Greater distinguishing information is held in the after-going slow wave than the sharp wave for the identification of clinical groups. Information analysis may assist in differentiating clinical syndromes from EEG signals.

Adult↗

Non-painful and painful stimulation of human skin and muscle: analysis of cerebral evoked potentials.

The present study compared the cerebral processing of non-painful and painful cutaneous CO2 laser stimulation and intramuscular electrical stimulation in 11 normal subjects. The overall wave form morphology of the long-latency evoked potentials (EPs) at the central vertex (Cz) was identical and surface topographic mappings of the 21-channel recordings showed similar distributions, suggesting involvement of common neural generators. However, the EPs caused by intramuscular stimulation differed from cutaneous stimulation in several distinct ways. First, the latency of the major positive and negative components were significantly shorter with intramuscular stimulation (N 128-145 ms; P 274-298 ms) compared to cutaneous stimulation (N 235-286 ms; P 371-383 ms) (P < 0.001). Second, the peak-to-peak amplitude and root-mean-square values of intramuscular EPs recorded at Cz showed a ceiling effect in the painful range, whereas the laser EPs continued to increase in this range. Third, painful intramuscular, but not non-painful, stimulation caused a frontal activity which not was observed with cutaneous laser stimulation at any intensity. Conduction velocity measurements indicated activation of nociceptive A-delta afferents with cutaneous laser stimulation (10.2 +/- 0.2 m/s) and activation of a mixed nerve fiber population with intramuscular electrical stimulation (65.8 +/- 25.8 m/s). Differences between laser and intramuscular EPs may be due to different types and origins of activated afferent fibers. Laser EPs can be used specifically to assess cutaneous A-delta fiber function, whereas intramuscular EPs reflect the cerebral processing of a mixed afferent input from muscle tissue.

Adult↗

Relative value of the inion and mid-parietal locations as additional recording sites in pattern reversal visual evoked potentials.

Although the P100 response of pattern reversal visual evoked potentials (PRVEPs) is most commonly recorded from the midline occipital site (MO), the response at this location can occasionally be absent or poorly defined due to anatomical variability of the visual cortex. In these cases, the American Electroencephalographic Society Evoked Potential Guidelines recommends recording from the mid-parietal (MP) and Inion electrode sites. In this study, we compared the amplitude of the P100 component recorded simultaneously from MO, MP and the Inion. PRVEPs obtained following stimulation with 30' check sizes from 155 consecutive patients (310 eyes) over a 2 year period were analyzed. At each of the 3 recording sites, the peak amplitude of P100 was calculated as N75-P100, P100-N145, and the sum of N75-P100 and P100-N145. There was a statistically significant difference between the electrode sites for all 3 methods of amplitude measurement (one-way ANOVA; P < 0.0001). For each method of measurement, there was no significant difference between P100 amplitude at MO or the Inon, but a significantly reduced amplitude at MP compared to both the MO and Inion electrode sites (post hoc Scheffe, P < 0.05). The P100 amplitude was highest at the Inion in 18% of responses, including cases where the amplitude at that site was at least twice that at MO. In no case was the amplitude highest at MP. Our results indicate that the Inion is a better recording site compared to MP when acquiring PRVEPs, is often complementary to MO, and should be the first additional site to be used when extra channels are available.

Adolescent↗

Pain-related laser-evoked potentials in awake monkeys: identification of components, behavioral correlates and drug effects.

Cutaneous stimulation with CO2 laser pulses activates small diameter sensory afferents and evokes a pain-related potential best recorded from the vertex (Cz) of humans. We report here the first successful recording of pain-related laser evoked potentials (LEPs) from awake monkeys. Laser pulses with stimulus intensities adjusted to the lowest level giving reproducible cerebral responses were delivered to the shaved tail of three awake African green monkeys. The proximal and distal tail were stimulated to calculate the conduction velocity of the activated fibers. The effects of subcutaneous injections of morphine and cocaine on the LEPs were evaluated. The results indicate that reproducible LEPs, with a morphology similar to those obtained from humans, can be recorded from the awake monkey. The calculated conduction velocity of the activated fibers averaged 8.7 m/s, which is in the range of A delta fibers. Following subcutaneous morphine injections, the LEPs disappeared and were quickly restored to their baseline amplitude following administration of naloxone. Cocaine administered subcutaneously led to a significant attenuation of LEP amplitudes without producing behavioral sedation. These findings suggest that the LEPs recorded from monkeys represent analgesic-sensitive, nociceptive-related potentials similar to those recorded from humans.

Anesthetics, Local↗

Comparative psychophysical characteristics of cutaneous CO2 laser and contact heat stimulation.

Psychophysical visual analog scaling can be used to reveal critical determinants of the neural processing underlying non-painful and painful heat sensations produced by radiant and contact heat stimulation. This study determined the stimulus-response (S-R) functions of cutaneous non-painful and painful heat stimuli delivered by an infra-red CO2 laser or by a contact thermode in a series of experiments in healthy volunteers. In experiments 1 (n = 12), with the rating scale anchored at pain threshold, the S-R curve for brief (60 ms) laser pulse stimulation with a beam diameter of 10 mm was a negatively accelerating function. Transformation of laser stimulus intensity (W) into temperatures (degree C) did not change the form of the S-R curve. In experiment 2 (n = 9), using the same laser stimulus parameters as in experiment 1, but without an anchored rating scale, the form of the S-R relationship did not change. In experiment 3 (n = 9), increases of the laser pulse duration up to 5 s and the beam diameter up to 18 mm produced linear S-R curves. In contrast, in experiment 4 (n = 21), the S-R curve for cutaneous contact heat stimuli applied for 5 s with an 18 mm diameter probe was best described by a positively accelerating power function with an exponent greater than 2.0. These experiments have (1) characterized the S-R functions for different parameters of infra-red laser stimulation of the skin, and (2) have shown that the form of the S-R function for innocuous and noxious heat sensation is influenced strongly by the physical conditions of heat stimulus application, including mechanical contact with the skin.

Adolescent↗