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Biomedical subjects

R H Mattson

Publications and source records attributed to R H Mattson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics.

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.

Automatism↗
PubMed1998

Medical management of epilepsy in adults.

Optimal treatment of epilepsy in adults requires a tailored approach that weighs the efficacy of individual drugs in the specific diagnosis against the patient's risks for adverse events. Partial seizures, which are the most common seizure type in adults, can be effectively controlled by virtually all the standard and newer antiepileptic drugs (AEDs). For the generalized epilepsies, valproate remains the drug of choice. Data continue to accumulate regarding use of the newer agents. Overall, many of the newer AEDs may offer a better tolerability than the standard agents because of more favorable pharmacokinetic characteristics and lack of interactions with drugs other than AEDs. Serious adverse events have been associated with felbamate and lamotrigine, however, and more experience is needed with many of the other newer AEDs to better define their safety profiles. Monotherapy should be the goal when AED treatment is instituted for the adult with epilepsy. Dosage modification on the basis of seizure control and toxicity should be implemented, as well as single-drug trials with alternative AEDs, before resorting to polytherapy. With the introduction of several promising newer AEDs, safe and effective seizure control may become a reality for an increasing number of adults with epilepsy.

Adult↗
PubMed1998

Novel methods for studying new antiepileptic drug pharmacology.

A number of new antiepileptic drugs act by indirect mechanisms and thus produce effects that may not best be measured by traditional blood studies of the drugs and their metabolites. Study of the indirect action of these drugs on GABA-mediated inhibition by microdialysis and nuclear MR spectroscopy has proved more relevant. These new investigative techniques may also prove valuable as compounds affecting glutamate or other excitatory neurotransmitters are developed.

Animals↗
PubMed1996

Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group.

OBJECTIVE: To assess the effects of carbamazepine vs valproate sodium on cognitive functioning in patients with epilepsy compared with normal control subjects. DESIGN: Patients with recently diagnosed, previously unmedicated seizures participated in a prospective randomized double-blind Department of Veterans Affairs multicenter study of the efficacy and toxicity of carbamazepine vs valproate. MAIN OUTCOME MEASURE: A behavioral toxicity battery was administered prior to treatment and again 6 and 12 months after the initiation of antiepileptic medication. RESULTS: There were no significant differences in the effect of carbamazepine vs valproate on motor speed and coordination, memory, or concentration and mental flexibility, and there was no significant decline in neuropsychological performance from pretreatment baseline levels for either drug. No significant differences in performance were found between patients with low (mean, 52.8 micrograms/mL) vs high (mean, 94.4 micrograms/mL) serum valproate levels within the therapeutic range. Patients treated with either carbamazepine or valproate did not show practice effects experienced by normal controls, a finding that may reflect a subtle compromise in cognitive functioning. CONCLUSION: The impact of carbamazepine and valproate monotherapy on cognitive functioning is similar: both drugs produce minimal negative effects compared with pretreatment baseline performance.

Adult↗
PubMed1996

The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy.

Gabapentin has come into clinical use as adjunctive therapy in the treatment of epilepsy. Designed to mimic gamma-aminobutyric acid (GABA), its mechanism of action remains elusive. In vivo measurements of GABA in human brain were made using 1H magnetic resonance spectroscopy. We used a 2.1-T magnetic resonance imager-spectrometer and an 8-cm surface coil to measure a 13.5-cm3 volume in the occipital cortex. GABA levels were measured in 14 patients enrolled in an open-lbel trial of gabapentin. GABA was elevated in patients taking gabapentin compared with 14 complex partial epilepsy patients, matched for antiepileptic drug treatment. Brain GABA levels appeared to be higher in patients taking high-dose gabapentin (3,300-3,600 mg/day) than in those taking standard doses (1,200-2,400 mg/day). Gabapentin appears to increase human brain GABA levels.

Acetates↗
PubMed1996

Low brain GABA level is associated with poor seizure control.

Low gamma-aminobutyric acid (GABA) concentrations in the cerebrospinal fluid are seen in a variety of epileptic syndromes. Low GABA levels outside of the epileptic focus may facilitate spread of discharges beyond the focus. In vivo measurements of GABA were made by 1H spectroscopy using a 2.1-T magnetic resonance imager-spectrometer and an 8-cm surface coil to measure a 14-cm3 volume in the occipital lobe. Patients with complex partial seizures had lower GABA levels (1.03 mmol/kg of brain; 95% confidence interval [CI], 0.95-1.12; n = 28; p < 0.02) than did subjects without epilepsy (1.18; 95% CI, 1.13-1.24; n = 19). There was a significant association between low GABA levels and recent seizures (correlation coefficient of 0.548, p < 0.01, df of 32). Conversely, patients with well-controlled seizures had higher brain GABA levels than did patients with recent seizures. Patients with seizures within a day of the measurement had lower GABA levels (0.92 mmol/kg; 95% CI, 0.78-1.06; n = 7) than did patients who were seizure free for 5 years or longer (1.28; 95% CI, 1.09-1.47; n = 4). Poor seizure control is associated with low brain GABA levels.

Adult↗
PubMed1996

Human brain gamma-aminobutyric acid levels and seizure control following initiation of vigabatrin therapy.

Vigabatrin is a novel antiepileptic drug designed to control seizures by raising brain gamma-aminobutyric acid (GABA) concentrations. Seizure control is not improved significantly when the daily dose is increased beyond 50 mg/kg. Serial, in vivo measurements of GABA levels in human occipital lobe were made using 1H NMR spectroscopy before and after the start of vigabatrin treatment. We used a 2.1-T magnetic resonance imagerspectrometer and an 8-cm surface coll to examine serially a 14-cm3 volume in the occipital lobe of 26 patients with complex partial seizures. Brain GABA content increased following the start of vigabatrin treatment up to a daily dose of 60 mg/kg. Additional increases in dose falled to increase brain GABA content further. GABA synthesis may decrease with sustained elevations of human brain GABA levels. Starting vigabatrin treatment reduced seizure frequency by > 50%, from six to seven per month to three. Improved seizure control was not associated with further increases of vigabatrin dose. Increased brain GABA concentration was associated with improved seizure control. Starting vigabatrin treatment improved seizure control twofold when GABA levels increased above 1.8 mmol/kg. Further increases in brain GABA content above 2.5 mmol/kg provided less protection. Measuring occipital lobe GABA concentrations may predict improved seizure control when using antiepileptic drugs designed to increase brain GABA levels.

Adult↗
PubMed1996

The role of the old and the new antiepileptic drugs in special populations: mental and multiple handicaps.

Epilepsy is common in individuals who are mentally retarded and/or otherwise multiply handicapped. These patients often display several seizure types. Seizure control may be difficult and drug interactions common because of polytherapy. Cognitive, behavioral, affective, and motor problems in these patients often confound accurate diagnosis and effective management. Treatment often requires not only antiepileptic drugs (AEDs) but also psychoactive drugs and/or environmental and personal support. To minimize unwanted drug effects, therapeutic strategies should focus on the administration of the fewest possible drugs at the lowest effective dose. The new AEDs may be of special value at times in these populations because they offer potential for improved efficacy, but especially because many of them provide better safety profiles and fewer pharmacokinetic interactions with other drugs.

Acetates↗
PubMed1996

Human brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose.

Using 1H spectroscopy, we measured occipital lobe GABA levels serially in 18 patients enrolled in an ongoing open label trial of vigabatrin. Brain GABA levels were elevated twofold in patients taking vigabatrin (3 to 4 g/d) compared with nonepileptic subjects. Serial measurements suggested that brain GABA rose in proportion to vigabatrin dose up to 3 g/d. Doubling the dose from 3 to 6 g/d failed to increase brain GABA further. Serial measurements on three patients taking 6 g/d showed a gradual decrease in brain GABA in two patients over 1 to 2 years of treatment. These observations suggest that GABA synthesis may decrease at high GABA levels.

Adult↗
PubMed1996

Parenteral antiepileptic/anticonvulsant drugs.

A large number of drugs can be given parenterally for the control of acute seizures, although many of these compounds are associated with serious adverse effects. Phenobarbital, the first antiepileptic drug (AED), has long been available in an injectable formulation. The sodium salt of phenobarbital is water soluble, and its parenteral formulation can be given for maintenance therapy or treatment of acute seizures. The introduction of phenytoin in 1938, and its subsequent parenteral formulation, represented a significant advance in AED therapy owing to its relative absence of sedation. However, the risk of adverse effects necessitates that the rate of phenytoin administration usually be limited to 50 mg/min. I.v. valproate has been used extensively but has not been approved for use in the United States, and its value for treating acute seizures is unclear. Several benzodiazepines have been used as adjunctive drugs for the treatment of epilepsy; given parenterally, they provide rapid CNS entry and prompt control of seizures, but their effect is short lived. Agents that have more hypnotic anesthetic properties are often used when the benzodiazepines or phenytoin alone or in combination fails.

Anticonvulsants↗
PubMed1996

Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group.

BACKGROUND: Two prospective observations of adults with symptomatic, localization-related (partial) epilepsy included 1,102 patients in VA multicenter studies (VA-118 and VA-264). Analyses assessed the likelihood of remaining seizure free for 12 and 24 months after initiating adequate antiepileptic drug therapy. METHODS: Patients were grouped as having only secondarily generalized tonic-clonic seizures (GTC), only complex partial seizures (CPS), or both types (MIXED) at entry. The cumulative proportion of patients remaining seizure free with standard antiepileptic drug therapy was determined by actuarial life table methods. RESULTS: At 12 months, 70% and 61% of GTC patients (VA-118 and VA-264, respectively) had no further GTC; 53% and 50% of MIXED, predominantly GTC patients had no further GTC, 21% and 28% of CPS patients had no further CPS and 98% and 91% were seizure free for GTC; 32% and 35% of MIXED, predominantly CPS patients had no further CPS, and 62% and 51% of patients with MIXED seizure types remained seizure free for CPS for 12 months after enrollment. CONCLUSIONS: The overall prognosis for control of seizures of any type for 12 months was best for those who had only GTC at entry (55% and 48%), worst for those who had only CPS at entry (23% and 26%), and intermediate for those with MIXED seizures at entry (32% and 25%) (all p < 0.0001). Prognosis can be based on the predominant seizure type in patients with multiple types.

Adult↗
PubMed1996

Human brain GABA levels rise rapidly after initiation of vigabatrin therapy.

OBJECTIVE: The purpose of this study was to measure changes in brain GABA after a single oral dose (50 mg/kg) of vigabatrin in patients with intractable epilepsy. BACKGROUND: Vigabatrin is a safe and effective antiepileptic medication designed to increase brain GABA by irreversibly inhibiting GABA-transaminase. Serial measurements showed that brain GABA levels increased from 1.0 (SEM, 0.07) to 2.4 mmol/kg (SEM, 0.09) in patients who were regularly taking vigabatrin (50 mg/kg/day divided into two doses). METHODS: In vivo measurements of GABA in human brain were made using 1H magnetic resonance spectroscopy. We used a 2.1-T NMR spectrometer and an 8-cm surface coil to measure a 13.5 cm3 volume in the occipital cortex. RESULTS: Brain GABA increased by more than 40% within 2 hours of administration of a single 50 mg/kg oral dose of vigabatrin from 0.95 (SEM, 0.07; n = 7) to 1.34 mmol/kg (SEM, 0.13). By the next day, brain GABA increased further to 1.44 mmol/kg (SEM, 0.08). Levels declined gradually to 1.16 mmol/kg (SEM, 0.14) by day 5 and 1.03 mmol/kg (SEM, 0.10) at day 8. The patients reported no side effects and were calm but not drowsy. CONCLUSIONS: A single oral dose of vigabatrin rapidly increased brain GABA without side effects. Once-a-day dosing should be as effective as divided doses.

Administration, Oral↗
PubMed1995

Near-patient rapid assay of phenytoin concentration.

The Biotrack 516 is a simple, automated whole blood phenytoin (PHT) assay that reports corresponding total serum concentrations in 3 min. We compared Biotrack results in 58 patients with the total and unbound serum PHT concentrations measured by the standard TDx fluorescence polarization immunoassay. Correlation with total TDx concentration was high (r = 0.98); median absolute error was 1.4 micrograms/ml. Correlation of unbound PHT with Biotrack (r = 0.95) was comparable to correlation of unbound and total TDx (r = 0.94). The Biotrack assay is a promising method for clinical monitoring of PHT concentrations.

Adolescent↗
PubMed1995

Initial observations on effect of vigabatrin on in vivo 1H spectroscopic measurements of gamma-aminobutyric acid, glutamate, and glutamine in human brain.

Recent developments involving 1H nuclear magnetic resonance (NMR) spectroscopic editing techniques have allowed noninvasive measurements of gamma-aminobutyric acid (GABA) in human cerebrum. The additional information gained from GABA and macromolecule measurements permitted more precise glutamate (Glu) and glutamine (Gln) measurements. Occipital lobe GABA in 10 nonepileptic, healthy subjects was 1.0 mumol/g brain [95% confidence interval (CI) 0.9-1.1]. Vigabatrin (VGB) is a safe and effective antiepileptic drug (AED) that irreversibly inhibits neuronal and glial GABA-transaminase. GABA levels were increased in all patients treated with VGB. With a standard dose of 3-6 g/day, GABA levels were 2.6 mumol/g (95% CI 2.3-2.8). Mean occipital GABA level measured in epileptic patients not receiving VGB was 0.9 mumol/g (95% CI 0.7-1.1). Gln was increased by 1.9 mumol/g and Glu was decreased by 0.8 mumol/g in patients receiving VGB as compared with patients receiving standard medications alone.

Adult↗
PubMed1995

Successful epilepsy surgery without intracranial EEG recording: criteria for patient selection.

Twenty-two patients with intractable complex partial seizures (CPS) were treated with temporal lobectomy. Eighteen of 22 (82%) are seizure-free while receiving medication, with a mean follow-up time of 4 years. In each case, the clinical seizure pattern, interictal and ictal scalp EEG, magnetic resonance imaging (MRI), neuropsychological testing, and results of the intracarotid amobarbital procedure (IAP) converged to indicate a localized abnormality. None of the patients in this series had mass lesions, vascular malformations, or cortical scars, but 18 of 22 had hippocampal atrophy on MRI and 20 had hippocampal sclerosis (HS) on pathologic examination. We believe it is possible, on the basis of the preoperative evaluation described, to identify a population of epileptic patients who will do very well postoperatively. Such patients do not require invasive EEG monitoring, and they represent approximately 20% of the patients treated surgically in our epilepsy unit in the past several years.

Adolescent↗