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Biomedical subjects

M A Mikati

Publications and source records attributed to M A Mikati.

At least 37 records · Page 2Linked to original sources
PubMed1996

Differential diagnosis of staring spells in children: a video-EEG study.

Staring is frequently a nonepileptic manifestation in children. To differentiate epileptic versus nonepileptic staring, we reviewed clinical and video-EEG findings in 143 patients, aged 5 months to 43 years, monitored for staring episodes. In 79 patients staring was of epileptic origin; 46 had partial seizures and 33 atypical absence. Thirty-five had behavioral staring, 8 psychogenic seizures, 1 a migraine equivalent, and in 20 no staring spells were recorded. In all patients with epileptic staring, epilepsy was suspected clinically. Only 22 of the admissions for behavioral staring and 3 for pseudoseizures were to exclude a possible nonepileptic phenomenon. Review of their clinical histories revealed that certain findings strongly support a nonepileptic origin. In conclusion, a careful clinical history will differentiate between epileptic and nonepileptic staring episodes in most patients. Video-monitoring is helpful to adjust treatment or to exclude nonepileptic events in patients with refractory staring spells.

Adolescent↗
PubMed1996

Efficacy of gabapentin therapy in children with refractory partial seizures.

Thirty-two children with refractory partial epilepsy received open-label gabapentin as an additional medication to their antiepileptic drug regimen. Gabapentin was given in a dose ranging from 10 to 50 mg/kg per day (mean dose, 26.7 mg/kg daily). All patients had partial seizures with or without secondary generalization. Compared with baseline, 11 patients (34.4%) had a greater than 50% decrease in seizure frequency, and 4 (12.5%) had a 25% to 50% decrease in seizure frequency. Of the seven children who received the medication for 6 months or longer, two were seizure free and four were almost seizure free (having one seizure every few months). Mean gabapentin concentration was 4.8 micrograms/ml, and mean apparent clearance was 372 ml/kg per hour. The major reported side effects were behavioral. These consisted of hyperactivity, irritability, and agitation that occurred in patients with baseline mental retardation with attention deficit. We conclude that gabapentin can be a useful adjunctive medication in the treatment of refractory partial epilepsy in children.

Acetates↗
PubMed1996

Pharyngeal dysesthesia as an aura in temporal lobe epilepsy.

PURPOSE: Because oral, buccal, and sometimes oral-pharyngeal manifestations in epilepsy are linked to the central-temporal region, we studied 3 patients with childhood-onset partial seizures that consistently began with pharyngeal dysesthesias, described as either throat tingling or burning, to localize seizure onset. METHODS: Because of an intractable clinical course, each patient underwent invasive video-EEG monitoring, which localized the epileptogenic zone to the mesial temporal lobe. The 3 patients underwent temporal lobe resections. RESULTS: All 3 patients achieved remission of the pharyngeal auras and a 90-100% reduction in the frequency of their seizures. CONCLUSIONS: Pharyngeal dysesthesias can be the initial manifestation of complex partial seizures (CPS) of temporal lobe origin.

Adolescent↗
PubMed1996

Behavioral side effects of gabapentin in children.

We report 7 children who received gabapentin (GBP) as adjunctive medic ation and subsequently developed behavioral side effects. These behavioral changes consisted of intensification of baseline behaviors as well as new behavioral problems. Behaviors that parents considered most troublesome were tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioral changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder and developmental delays.

Acetates↗
PubMed1995

Effect of kainic acid-induced status epilepticus on inositol-trisphosphate and seizure-induced brain damage in mature and immature animals.

We investigated the role of excitatory amino acids in the activation of the phosphoinositide pathway during kainic acid-induced seizures in mature and immature animals. Kainic acid caused more severe seizures in the immature animals, but no hippocampal damage or induction of phosphoinositide hydrolysis. In mature animals, seizures were mild but severe hippocampal damage was seen and was associated with a marked and sustained release of inositol-trisphosphate, suggesting a role of this pathway and intracellular calcium stores in seizure-induced brain damage.

Aging↗
PubMed1995

EEG prior to hemispherectomy: correlation with outcome and pathology.

Hemispherectomy, for the treatment of seizures, is highly successful but has a significant morbidity rate. The procedure is usually restricted to patients with an intractable seizure disorder and hemiparesis. Because of the inherent risk of surgery, patient selection is a critical issue. This report describes the evaluation of background activity and ictal patterns on surface and invasive EEG in 12 children who underwent both anatomical (7) and functional (5) hemispherectomy in order to determine the role of electroencephalography in the selection of patients for hemispherectomy, and to correlate EEG findings with underlying pathology and outcome. A favorable outcome was predicted by an interictal EEG with two or more of the following: suppression over the abnormal hemisphere, absence of contralateral slowing, absence of generalized discharges and absence of bilateral independent spiking; or by unilateral onset of ictal discharges on invasive intracerebral EEG recording. Outcome did not correlate with the underlying pathology. Hemispherectomy can be successful in patients with a variety of predominantly unilateral pathologic entities.

Brain↗
PubMed1995

Psychogenic seizures: video telemetry observations in 27 patients.

Psychogenic seizures are unusual during the first decade of life. To compare the clinical features of psychogenic seizures in young children with those of teenagers, the long-term electroencephalographic and video monitoring studies of all patients younger than 18 years of age with recorded episodes diagnosed as psychogenic seizures were reviewed from a single hospital during the past 7 years. The 27 patients were divided into 2 age groups: group A, 6-9 years (n = 5), and group B, 10-17 years (n = 22). All patients had habitual episodes recorded during monitoring. Although the adolescents displayed clinical patterns similar to adult patients with psychogenic seizures, the children demonstrated a clinical pattern characterized mainly by prolonged staring and unresponsiveness. The most common behaviors in the adolescent group were tremor (45%), intermittent stiffening (41%), and out-of-phase movements of the extremities (36%). Fifteen percent of the patients had a history of seizures. This study suggests that young children with psychogenic seizures have clinical profiles different from that of teenagers.

Adolescent↗
PubMed1995

Pseudoseizure manifestations in two preschool age children.

We report two patients with epilepsy with pseudoseizures at age 6 years. Both presented with intractable staring spells. Pseudoseizures were provoked and aborted by suggestion, leading to the diagnosis. In both patients, evidence of a neuropsychological disturbance was later found and psychotherapy started. Monitoring of intractable staring episodes is recommended prior to escalating antiepileptic drug levels or resorting to polytherapy. In addition, differentiation from other non-epileptic phenomena is necessary to initiate proper therapy.

Anticonvulsants↗
PubMed1994

Phenobarbital modifies seizure-related brain injury in the developing brain.

To investigate the potential role of drug therapy in preventing or exacerbating seizure-related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before or 1 day after kainic acid was administered, and was continued through postnatal day 153. Rats receiving phenobarbital had therapeutic concentrations during most of the 24-hour dosing period, but also experienced supratherapeutic peak concentrations. The animals were subsequently tested using the water maze (a measure of visuospatial memory), open field (a measure of activity level), and handling tests (a measure of emotionality). The frequency of spontaneous recurrent seizures was monitored during and after phenobarbital therapy. Kainic acid resulted in status epilepticus on postnatal day 35 in all the rats that received it but those receiving phenobarbital first manifested a shorter and less severe status epilepticus as compared to the rats given kainic acid alone. Rats starting phenobarbital immediately before kainic acid was administered did not differ from control rats on behavioral testing and had no subsequent spontaneous recurrent seizures and no histological lesions. Rats receiving kainic acid alone performed significantly poorer than did control rats in the water maze, were more aggressive, had histological lesions, and manifested spontaneous recurrent seizures. As compared to the group treated only with kainic acid, rats receiving kainic acid followed by phenobarbital at postnatal days 36 to 153 manifested similar aggressiveness and histological lesions, similar frequency of spontaneous recurrent seizures after phenobarbital taper, and even greater disturbances in memory, learning, and activity level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Technetium-99m HmPAO brain SPECT and outcome of hemispherectomy for intractable seizures.

With recent descriptions of the modified hemispherectomies and hemicorticectomy, there has been renewed interest in hemispherectomy for treatment of intractable seizures with hemiparesis. Because long-term outcome remains uncertain, patient selection remains difficult. 99mTc-HmPAO brain SPECT has been a helpful adjunct in the evaluation of epilepsy surgery candidates. We report SPECT scan findings in 7 patients who underwent hemispherectomy and compare these results with scalp EEG findings. Six patients had unilateral SPECT findings and all had a favorable outcome, regardless of surface EEG findings.

Adolescent↗
PubMed1994

Long-term behavioral deficits following pilocarpine seizures in immature rats.

The effect of seizures on subsequent long-term behavior was studied in immature rats. A similar severity of seizures were induced in 20-day old rats (P20) and 45-day old rats (P45) by intraperitoneal injections of pilocarpine at doses of 200 mg/kg and 380 mg/kg, respectively. Immediately after injection of pilocarpine, prolonged seizures with electroencephalographic ictal discharges were observed in both groups of rats. These seizures were followed by seemingly complete neurological recovery. In rats that received pilocarpine at P45 spontaneous recurrent seizures appeared after 4-10 days and persisted until completion of the study at P100. Behavioral tests performed when the rats were fully mature demonstrated that they were more aggressive when handled, more active in open field, and had deficits in learning platform position in the water maze as compared to controls. Furthermore, flurothyl seizure latency was significantly lower in pilocarpine-treated P45 rats than controls. Histology examination showed gross cell loss in the CA3 subfield of the hippocampus in four out of six pilocarpine-treated rats while no cell loss was found in control rats. Rats that received pilocarpine at P20, despite having more severe seizures than the P45 rats, had no histological lesions, did not develop spontaneous recurrent seizures, and had no significant difference in the flurothyl seizure latency test when compared to their controls. While there was no difference between the control and pilocarpine-treated rats in the handling and open field test, P20 rats receiving pilocarpine were slower in learning platform position in the water maze than the controls. Rats receiving pilocarpine at P45 performed significantly more poorly than rats treated at P20 in the water maze. These results suggest that prolonged seizures in immature rats can cause long-term behavioral deficits. However, the severity and nature of these deficits are highly age dependent.

Animals↗
PubMed1994

Efficacy of felbamate in therapy for partial epilepsy in children.

Thirty children (2 to 17 years of age) with refractory partial seizures received open-label felbamate as an add-on medication to their background antiepileptic drugs. The dose was increased up to a maximum of 45 mg/kg. Compared with baseline seizure activity, there was a 53% decrease in seizure frequency during felbamate therapy; 50% of the patients had more than a 50% decrease in seizure frequency. Patients older than 10 years of age were more likely to have a favorable response. Age correlated positively with felbamate concentrations and negatively with apparent felbamate clearance. Transient weight loss occurred in 57% of the patients; the weight loss was maximal after 12 weeks of initiation of felbamate, and subsided after the twentieth week of treatment. Anorexia and insomnia were reported in 20% and 16% of the patients, respectively. Adverse effects were generally tolerable; felbamate therapy was discontinued because of side effects in only one patient, because of a rash. We conclude that felbamate can be a useful and well-tolerated medication in the treatment of refractory partial epilepsy in children. However, increased apparent clearance of this drug in younger children should be considered in treatment of this age group.

Adolescent↗
PubMed1993

Effects of quisqualic acid and glutamate on subsequent learning, emotionality, and seizure susceptibility in the immature and mature animal.

To compare the long-term behavioral effects of chronic administration of excitatory amino acids in the mature and immature brain quisqualic acid (QA) and glutamate (GLU) were administered intraventricularly by osmotic pumps over 7 days in 20- and 60-day-old rats. Both age groups received identical dosages of QA or GLU. At age 90 days, all animals were assessed for abnormalities of learning and memory using the Morris water maze, emotionality using the handling test, and seizure threshold using flurothyl inhalation. No significant differences were found in either the water maze or handling test. However, 60-day-old rats receiving QA or GLU had more spontaneous seizures than the 20-day-old rats. In both age groups histological damage following QA and GLU was limited to the ipsilateral hippocampus, was maximum at the site of the catheter tube, and was similar in the two age groups studied. The adverse effects of long-term effects of chronic exposure to excitatory amino acids are similar in the immature and mature brain.

Administration, Inhalation↗
PubMed1993

Effects of kindling on subsequent learning, memory, behavior, and seizure susceptibility.

To determine the long-term effects of seizures on the developing brain we kindled 20-, 40-, and 60-day-old rats to stage 5 seizures and then elicited an additional 15 seizures using the same kindling stimulation. At age 80 days, all animals that reached stage 5 kindling, and their respective age-matched controls, underwent behavioral testing using the Morris water maze, open field test, and handling test. Prior to euthanasia the animals had seizure threshold tested using flurothyl inhalation. No differences were noted in time to platform in the water maze or activity level in the open field test between the kindled rats and controls in any of the three age groups. Rats kindled at age 20 and 40 were more emotional than the controls in the handling test. In the flurothyl inhalation test, rats kindled at 40 and 60 days of age had a shorter latency to all seizures stages than the controls. These results demonstrate that while kindling results in no alteration of learning, memory, or activity level, it does result in altered emotionality and activity level in immature animals, as well as reduced seizure threshold in pubescent and mature rats. The animal model used appears to be an important variable in determining the long-term effects of seizures.

Administration, Inhalation↗
PubMed1992

Effect of high doses of intravenously administered immune globulin on natural killer cell activity in peripheral blood.

Because Kawasaki disease is a disorder characterized by lymphocyte activation and immune complex destruction of endothelial cells, we examined the effect of administration of high doses of intravenously administered immune globulin (IVIG) on a lymphocyte population with affinity for endothelial cells: the natural killer cells. We found that administration of high doses of IVIG resulted in a significant increase in the activity of natural killer cells and in the numbers of circulating CD16+ cells. Furthermore, a study of patients treated with IVIG for seizure disorders suggests that this effect of IVIG on circulating NK cells is not unique to patients with Kawasaki disease. The beneficial effect of IVIG in the treatment of Kawasaki disease may be due to the ability of IVIG to inhibit interaction between natural killer cells and endothelial cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

A syndrome of autosomal dominant alternating hemiplegia: clinical presentation mimicking intractable epilepsy; chromosomal studies; and physiologic investigations.

We report the familial occurrence and apparent autosomal dominant inheritance of alternating hemiplegia of childhood. The proband, a 9-year-old boy, presented with developmental retardation, rare tonic-clonic seizures, and frequent episodes of flaccid alternating hemiplegia that had been presumed to represent postictal paralysis. The hemiplegia spells, which started in his first year, did not respond to multiple antiepileptics. Between attacks, there was choreoathetosis and dystonic posturing. Father, brother, paternal uncle, and paternal grandmother had similar histories of alternating hemiplegia. Investigations included negative CT, metabolic, and coagulation studies. EEG and SPECT 99mTc exametazime scanning failed to reveal any significant slowing or any major changes in cortical perfusion during hemiplegia as compared with nonhemiplegic periods. The karyotype revealed a balanced reciprocal translocation, 46,XY,t(3;9)(p26;q34) in the patient, in all the affected living relatives, and in one apparently unaffected sibling. The asymptomatic mother had a normal karyotype. Analysis of DNA markers was consistent with the karyotype results. Both affected siblings were treated with and responded to flunarizine therapy, with a greater than 70% decrease in attack frequency. Documented flunarizine trough serum concentrations were 28.9 ng/ml in the proband and 6.6 ng/ml in his brother.

Adult↗
PubMed1991

Pyridoxine-dependent epilepsy: EEG investigations and long-term follow-up.

The EEG features and clinical correlates were investigated before, directly after, and on long-term follow-up after initiation of pyridoxine therapy in 6 patients with B6-dependent epilepsy. At each phase, the EEG provided important diagnostic and prognostic information. Pre-B6 3 neonates manifested a unique EEG pattern of generalized bursts of 1-4 Hz sharp and slow activity. This pattern has not been previously described in neonates with B6 dependency and in this age group appears to be highly suggestive of the diagnosis. Five patients experienced an apparent initial response to traditional antiepileptics. The parenteral pyridoxine test, performed in all 5, and repeated in 3, proved to be a highly reliable and reproducible diagnostic test. After 50-100 mg of B6 there was cessation of clinical seizures within minutes and of paroxysmal discharges within hours. On long-term follow-up (3-28 years) all 6 patients were seizure free on B6 (10-100 mg/day) monotherapy. Recurrences of seizures and of specific sequential EEG changes (background slowing, photoparoxysmal response, spontaneous discharges, stimulus-induced myoclonus, generalized seizures) occurred upon B6 withdrawal. Long-term prognosis correlated with the EEG. Two patients had persistently abnormal EEG backgrounds and were moderately to severely retarded, while 4 had normal EEGs with normal or near normal development.

Brain↗