Biomedical subjects

A Beydoun

Publications and source records attributed to A Beydoun.

At least 37 records · Page 2Linked to original sources

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

Monotherapy trials of new antiepileptic drugs.

A number of clinical trials that test the efficacy and safety of the newer antiepileptic drugs (AEDs) have recently been concluded. Two dose-response trials in inpatients with refractory partial seizures and outpatients with newly diagnosed partial epilepsy established the efficacy of gabapentin as monotherapy. Lamotrigine was found to have efficacy similar to that of phenytoin and carbamazepine (CBZ) and to be better tolerated than CBZ in patients with newly diagnosed epilepsy. It was also shown to have efficacy as monotherapy in partial seizures, based on the results of an active controlled trial, and in the treatment of absence seizures, based on the results of a responder-enriched study. Topiramate as monotherapy was found to be efficacious for treatment of partial-onset seizures, based on the results of a single-center dose-response trial. A dose-response trial that tested the efficacy of tiagabine monotherapy in patients with refractory partial epilepsy was uninformative. Oxcarbazepine was found to be safe and efficacious in four comparative trials in patients with newly diagnosed epilepsy as well as in one placebo-controlled inpatient trial in patients with refractory partial seizures.

Adolescent↗

PubMed1997

Cerebral processing of acute skin and muscle pain in humans.

The human cerebral processing of noxious input from skin and muscle was compared with the use of positron emission tomography with intravenous H2(15)O to detect changes in regional cerebral blood flow (rCBF) as an indicator of neuronal activity. During each of eight scans, 11 normal subjects rated the intensity of stimuli delivered to the nondominant (left) forearm on a scale ranging from 0 to 100 with 70 as pain threshold. Cutaneous pain was produced with a high-energy CO2 laser stimulator. Muscle pain was elicited with high-intensity intramuscular electrical stimulation. The mean ratings of perceived intensity for innocuous and noxious stimulation were 32.6 +/- 4.5 (SE) and 78.4 +/- 1.7 for cutaneous stimulation and 15.4 +/- 4.2 and 73.5 +/- 1.4 for intramuscular stimulation. The pain intensity ratings and the differences between noxious and innocuous ratings were similar for cutaneous and intramuscular stimuli (P > 0.05). After stereotactic registration, statistical pixel-by-pixel summation (Z score) and volumes-of-interest (VOI) analyses of subtraction images were performed. Significant increases in rCBF to both noxious cutaneous and intramuscular stimulation were found in the contralateral secondary somatosensory cortex (SII) and inferior parietal lobule [Brodmann area (BA) 40]. Comparable levels of rCBF increase were found in the contralateral anterior insular cortex, thalamus, and ipsilateral cerebellum. Noxious cutaneous stimulation caused significant activation in the contralateral lateral prefrontal cortex (BA 10/46) and ipsilateral premotor cortex (BA 4/6). Noxious intramuscular stimulation evoked rCBF increases in the contralateral anterior cingulate cortex (BA 24) and subsignificant responses in the contralateral primary sensorimotor cortex (MI/SI) and lenticular nucleus. These activated cerebral structures may represent those recruited early in nociceptive processing because both forms of stimuli were near pain threshold. Correlation analyses showed a negative relationship between changes in rCBF for thalamus and MI/SI for cutaneous stimulation, and positive relationships between thalamus and anterior insula for both stimulus modalities. Direct statistical comparisons between innocuous cutaneous and intramuscular stimulation with the use of Z scores and VOI analyses showed no reliable differences between these two forms of noxious stimulation, indicating a substantial overlap in brain activation pattern. The comparison of noxious cutaneous and intramuscular stimulation indicated more activation in the premotor cortex, SII, and prefrontal cortex with cutaneous stimulation, but these differences did not reach statistical significance. The similar cerebral activation patterns suggest that the perceived differences between acute skin and muscle pain are mediated by differences in the intensity and temporospatial pattern of neuronal activity within similar sets of forebrain structures.

Acute Disease↗

PubMed1997

Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a double-blind, concentration-response design clinical trial. Depakote Monotherapy for Partial Seizures Study Group.

This is the first randomized, double-blind, parallel-group, multicenter trial that evaluated the efficacy of divalproex sodium monotherapy by comparing seizure frequency in 143 patients with poorly controlled partial epilepsy randomly assigned to high (80 to 150 micrograms/mL; 555 to 1,040 mumol/L) or low (25 to 50 micrograms/mL; 175 to 345 mumol/L) plasma valproate groups. There was a statistically significant reduction from baseline in the 8-week frequency of complex partial (p = 0.001) and secondarily generalized tonic-clonic seizures (p = 0.018) for patients in the high, compared with the low, plasma valproate group. Compared with baseline, there was a 30% median reduction in complex partial seizures for patients in the high group and a 19% increase for those in the low group. The median reduction for secondarily generalized tonic-clonic seizures was 70% for patients in the high group compared with a 22% increase in the low group. Adverse events that occurred significantly more frequently in the high group included tremors, thrombocytopenia, alopecia, asthenia, diarrhea, vomiting, and anorexia. This study demonstrates the efficacy of divalproex sodium as monotherapy for the treatment of partial-onset seizures and supports its role as one of the first-line antiepileptic drug treatments for patients with partial epilepsy.

Adolescent↗

PubMed1997

Gabapentin monotherapy: II. A 26-week, double-blind, dose-controlled, multicenter study of conversion from polytherapy in outpatients with refractory complex partial or secondarily generalized seizures. The US Gabapentin Study Group 82/83.

This study evaluated gabapentin monotherapy in 275 patients with medically refractory complex partial or secondarily generalized seizures who were taking one or two antiepileptic drugs (AEDs). Following an 8-week baseline, patients received randomized dosages of gabapentin (600, 1,200, or 2,400 mg/d) during a 26-week double-blind phase comprising 2 weeks gabapentin add-on therapy, an 8-week AED taper, and a 16-week gabapentin monotherapy period. Patients exited the study if they experienced a protocol-defined exit event. Results of outcome measures, including time to exit, completion rate, and mean time on monotherapy, showed no significant differences among dosage groups. Possible reasons for this lack of a dose-response relationship include withdrawal seizures and the limited range of gabapentin dosages studied. Overall, 20% of patients completed the study. Completion rates were higher among patients who had discontinued one AED (23%) than two AEDs (14%), and higher among patients who were not withdrawn from carbamazepine (27%) than among those who were (16%).

Acetates↗

PubMed1996

Laser-evoked cerebral potentials and sensory function in patients with central pain.

Central pain syndromes (CPS) could be caused by disinhibition of spinothalamic excitability or by other central nervous system (CNS) changes caused by reduced spinothalamic function. To examine these possibilities, we studied 11 patients (ages 51-82 years) with unilateral central pain and with reproducible cerebral evoked vertex potentials in response to cutaneous stimulation of the normal side with pulses from an infra-red CO2 laser. All patients had normal tactile and kinesthetic sensation; one had slightly decreased vibratory sense bilaterally. All showed, from the unaffected (asymptomatic) side, laser evoked potentials (LEPs) with negative (N) components ranging from 208 to 280 msec peak latency (av: 240 +/- 6 SE msec) and peak amplitudes of 1-7 microV (av: 2.9 +/- 0.5 SE microV), followed, in all but 1 patient, by positive (P) potentials ranging from 288 to 370 msec peak latency (av: 319 +/- 7.7 SE msec) with peak amplitudes of 1-7 microV (2.8 +/- 0.5 SE microV). Laser stimulation of the affected (symptomatic) side in 5 patients evoked LEPs with N-P interpeak amplitudes that were within 20% of those evoked from the normal side. All but one of these patients had thresholds for warm, heat pain, and deep pain that were normal in comparison with the unaffected side. The excepted patient had the largest N-P interpeak amplitude asymmetry (18.5%) of this group. Ratings of laser pulse intensity were either symmetrical (n = 2) or increased on the affected side (n = 3) in these patients. In contrast, laser stimulation of the affected side failed to evoke either N or P potentials in 6 patients, all of whom had lateralized increased thresholds for warm, heat pain, or deep pain, or reduced ratings of laser pulse sensation. Although 1 patient had increased ratings of laser pulse sensation, the amplitude of the LEP was always reduced on the side of increased pain or heat threshold in these CPS patients (Fisher exact test: P = 0.015). These results reflect primarily a deficit in spinothalamic tract function and do not suggest excessive CNS responses to synchronous activation of cutaneous heat nociceptors in patients with CPS.

Aged↗

PubMed1995

Asymmetric hypsarrhythmia: clinical electroencephalographic and radiological findings.

Twenty-six children (16 boys and 10 girls) with hypsarrhythmia and infantile spasms (IS) were studied at the University of Michigan EEG Laboratory in a 4-year period. Six (2 boys, 4 girls), had asymmetric hypsarrhythmia with a preponderance of both slowing and epileptiform activity over one hemisphere. All 6 had the symptomatic form of IS, 4 with dysplastic conditions, 1 with porencephaly from a cerebral infarct, and 1 with hypoxicischemic encephalopathy. Five children had focal abnormalities on either physical examination or imaging studies. Four had the highest amplitude slowing and most epileptiform activity ipsilateral to the lesion, in 1, it was contralateral. Asymmetric hypsarrhythmia constituted 23% of cases with hypsarrhythmia examined at our EEG laboratory. The significant success in surgical therapy for some children with IS indicates the importance of identifying focal hemispheric abnormalities even if they are not apparent clinically. EEG may suggest focal changes not detected clinically or radiologically.

Brain↗

PubMed1995

Octreotide reduces perception of rectal electrical stimulation by spinal afferent pathway inhibition.

Octreotide reduces perception of rectal distension in normal volunteers and irritable bowel patients. To localize octreotide's site of action, perceptual and evoked potential responses to rectal electrical stimulation were tested in seven normal volunteers after double-blind octreotide (100 micrograms 2) or placebo. After octreotide, the currents needed to elicit threshold perception of square-wave impulses delivered to the rectum were 29% higher than after placebo. When electrical stimulation was delivered at constant currents 50% above threshold, rectal perception scores were significantly reduced after octreotide compared with placebo. Rectal electrical stimulation led to characteristic and reproducible cerebral evoked potentials. Octreotide had no effect on latencies, but reduced peak-to-peak amplitudes by 35% compared with placebo. Rectal electrical stimulation also led to characteristic and reproducible spinal evoked potentials. Octreotide had no effect on spinal latencies, but reduced peak-to-peak amplitudes by 51%. In conclusion, octreotide reduces perception of rectal electrical stimulation, which is associated with inhibition of cerebral and spinal evoked potential amplitude, indicating effects on spinal afferent pathways.

Adult↗

PubMed1995

Gabapentin: pharmacokinetics, efficacy, and safety.

Gabapentin is a new antiepileptic drug (AED) with an attractive pharmacokinetic profile. It is absorbed by an active and saturable transport system, and has a high volume of distribution. Gabapentin is not bound to plasma proteins, does not induce hepatic enzymes and is not metabolized. At steady state, it has a half-life of 6-8 h, and is eliminated unchanged by renal route with a plasma clearance proportional to the creatinine clearance. It is devoid of significant drug-drug interactions when administered with the established AEDs or with oral contraceptives. Gabapentin used as an add-on AED significantly reduced the frequency of partial seizures and secondarily generalized tonic-clonic seizures in three large double-blind, placebo-controlled, parallel-group clinical trails. It is well tolerated, with transient somnolence and dizziness being the most frequent adverse effects. Although the mechanism of action of gabapentin is not fully established, there is strong evidence to suggest a novel mechanism of action. Gabapentin is a unique and promising drug that could improve the quality of life of patients with epilepsy and is a welcome addition to the armamentarium of currently available AEDs for the treatment of patients with seizures of partial onset.

Acetates↗

PubMed1994

The pattern visual evoked potential. A multicenter study using standardized techniques.

The peak latency of the pattern-reversal visual evoked potential is a sensitive measure of conduction delay in the optic nerve caused by demyelination. Despite its clinical utility, the pattern-reversal visual evoked potential has not previously been used in multicenter clinical trials, presumably because of difficulty in standardizing conditions between centers. To establish whether the pattern-reversal visual evoked potential could be adequately standardized for use as a measure in multicenter therapeutic trials for optic neuropathy or multiple sclerosis, stimulus and recording variables were equated at four centers and pattern-reversal visual evoked potentials were recorded from 64 normal subjects and 15 patients with resolved optic neuritis. Results showed equivalent latency and amplitude data from all centers, suggesting that stimulus and recording variables can be satisfactorily standardized for multicenter clinical trials. N70 and P100 peak latencies and N70-P100 interocular amplitude difference were sensitive measures of resolved optic neuritis.

Adolescent↗

PubMed1993

Biopsy results in a kindred with Lafora disease.

We studied biopsy results in a kindred with the Lafora form of progressive myoclonic epilepsy. Four members of a family with known consanguinity presented as teenagers with seizures, myoclonus, dementia, and ataxia. After the diagnosis was established by brain biopsy in the first patient, many efforts were made to obtain a tissue diagnosis in the three other patients. Lafora bodies were absent in most of the skin biopsy specimens in three patients and in liver biopsy specimens from two patients. In cases of Lafora disease, where a reasonably certain clinical diagnosis can be established, supported by biopsy proof in some family members, repeated biopsy specimens even at advanced stages of the disease may be negative. These findings suggest that negative skin or liver biopsy specimens in patients with progressive myoclonic epilepsy should not exclude the diagnosis of Lafora disease.

Adolescent↗