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Biomedical subjects

Richard H Mattson

Publications and source records attributed to Richard H Mattson.

7 recordsLinked to original sources

Brain homocarnosine and seizure control of patients taking gabapentin or topiramate.

PURPOSE: To assess the relation between seizure control and brain homocarnosine and gamma-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy. METHODS: In vivo measurements of GABA and homocarnosine were made of a 14-cc volume in the occipital cortex by using (1)H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied. RESULTS: Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not. CONCLUSIONS: In the visual neocortex, which is remote from the presumed seizure-onset zone, higher homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.

Adult↗

Fractures, epilepsy, and antiepileptic drugs.

The risk for skeletal fractures in patients with epilepsy is two to six times greater than in the general population. Fractures may be caused by seizures themselves or by falls, with or without seizures. Side effects of antiepileptic drugs (AEDs), such as ataxia, and coexisting neurological deficits contribute to the risk for falls. The effects of older AEDs on bone mineral density probably increase the risk for fractures associated with seizures and falls. Preventive measures include optimal control of seizures and supplementation with calcium and vitamin D. Whether newer AEDs prove to be without adverse effects on bone mineral metabolism remains to be determined.

Anticonvulsants↗

Cognitive, affective, and behavioral side events in adults secondary to antiepileptic drug use.

Antiepileptic drugs (AEDs) may contribute to and aggravate problems of cognition, mood, and behavior in some patients. The frequency and severity of the psychological disturbances are difficult to determine because many factors confound the interpretation of evidence whether it results from open case reports, controlled clinical trials, or neuropsychological testing. Concern about potential problems should not preclude trying an AED if other properties make the agent otherwise appropriate because the occurrence of adverse effects is often unpredictable in any given individual. Impairment can be minimized by gradual titration of dose and limiting total dose as clinically possible. If psychological problems arise and fine titration of the AED cannot eliminate the problem, the drug can be discontinued without permanent life threatening sequellae.

Adult↗

Novel LGI1 mutation in a family with autosomal dominant partial epilepsy with auditory features.

Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare idiopathic epilepsy syndrome caused by mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene. The authors report that molecular genetic studies in seven affected family members identified a novel F318C substitution that alters a highly conserved residue in a predicted repeat domain of unknown function. This report suggests that this domain may participate in the development of the ADPEAF phenotype.

Aged↗

Interlaboratory variability in the quantification of new generation antiepileptic drugs based on external quality assessment data.

PURPOSE: To assess interlaboratory variability in the determination of serum levels of new antiepileptic drugs (AEDs). METHODS: Lyophilised serum samples containing clinically relevant concentrations of felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), the monohydroxy derivative of oxcarbazepine (OCBZ; MHD), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were distributed monthly among 70 laboratories participating in the international Heathcontrol External Quality Assessment Scheme (EQAS). Assay results returned over a 15-month period were evaluated for precision and accuracy. RESULTS: The most frequently measured compound was LTG (65), followed by MHD (39), GBP (19), TPM (18), VGB (15), FBM (16), and TGB (8). High-performance liquid chromatography was the most commonly used assay technique for all drugs except for TPM, for which two thirds of laboratories used a commercial immunoassay. For all assay methods combined, precision was <11% for MHD, FBM, TPM, and LTG, close to 15% for GBP and VGB, and as high as 54% for TGB (p < 0.001). Mean accuracy values were <10% for all drugs other than TGB, for which measured values were on average 13.9% higher than spiked values, with a high variability around the mean (45%). No differences in precision and accuracy were found between methods, except for TPM, for which gas chromatography showed poorer accuracy compared with immunoassay and gas chromatography-mass spectrometry. CONCLUSIONS: With the notable exception of TGB, interlaboratory variability in the determination of new AEDs was comparable to that reported with older-generation agents. Poor assay performance is related more to individual operators than to the intrinsic characteristics of the method applied. Participation in an EQAS scheme is recommended to ensure adequate control of assay variability in therapeutic drug monitoring.

Anticonvulsants↗

Overview: idiopathic generalized epilepsies.

The idiopathic generalized epilepsies (IGEs) are an underemphasized topic. Two reasons for this relative lack of attention are that these epilepsies tend to be more easily controlled than the symptomatic partial and generalized epilepsies, and they are not as common. Because IGE usually arises in childhood or adolescence, these epilepsies may be thought of as a pediatric problem. However, a large number of patients continue to have seizures in adult life. Many exciting developments in understanding the pathophysiology, genetic etiology, and expanded treatment options warrant a reexamination of this important group of the epilepsies. This article reviews the more common IGE syndromes and associated seizure types as the first step in identifying the recent advances in our knowledge of these syndromes.

Adolescent↗

Frontal lobe tumoral epilepsy: clinical, neurophysiologic features and predictors of surgical outcome.

PURPOSE: To review the clinical, neurophysiologic features and surgical outcomes in patients with frontal lobe tumors and chronic intractable seizures. METHODS: Medical records of patients with intractable epilepsy who underwent resection or stereotactic biopsy of frontal lobe tumor (confirmed by surgical pathology) seen between 1985 and 1999 at Yale University School of Medicine Epilepsy Center were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, use of anticonvulsants, extent of surgery, pathological diagnosis, and tumor recurrence. RESULTS: Thirty-seven patients were included. Mean age at seizure onset was 31.6 years, and at tumor diagnosis was 36.2 years. Mean duration between onset of seizures and tumor diagnosis was 6.1 years. Seventeen patients had auras. Seizure frequency averaged 7.6 seizures per week, with 58% of patients having more than one seizure type. All patients used anticonvulsants, with 90% eventually using polytherapy. All patients eventually underwent at least one surgical procedure. Only 13 (35.1%) patients were class I. Twelve (32.4%) patients were class II, seven (18.9%) class III, and five (13.5%) class IV. No statistically significant differences were seen between good and poor long-term seizure outcome in relation to specific tumor pathology, seizure types, or type of resection. CONCLUSIONS: Long-term surgical outcomes in tumoral frontal lobe epilepsy are more favorable than those in nontumoral intractable frontal lobe epilepsy (65% class I or II) and less favorable than those in other tumoral epilepsy (overall, 70% class I). Frontal location of intracranial neoplasm may predict a less favorable long-term epilepsy prognosis than tumoral epilepsy in general, an observation for which several explanations are proposed.

Adolescent↗