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Biomedical subjects

G L Krauss

Publications and source records attributed to G L Krauss.

At least 19 recordsLinked to original sources

A controlled study comparing visual function in patients treated with vigabatrin and tiagabine.

OBJECTIVE: Vigabatrin treatment is frequently associated with irreversible retinal injury and produces retinal electrophysiological changes in nearly all patients. Concern has been raised that tiagabine and other antiepilepsy drugs (AEDs) that increase brain gamma-aminobutyric acid (GABA) might produce similar electrophysiological and clinical changes in visual function. The study compared visual function between groups of patients with epilepsy treated long term with tiagabine, vigabatrin, and patients treated with other AEDs. METHODS: A cross sectional study comparing visual acuity, colour vision, static and kinetic perimetry, and electroretinograms between groups of patients treated with tiagabine, vigabatrin, and other AEDs (control patients). Patients were adults receiving stable AED treatment for >6 months. RESULTS: Vigabatrin treated patients had marked visual field constrictions in kinetic perimetry (mean radius 39.6 degrees OD, 40.5 degrees OS), while tiagabine patients had normal findings (mean 61 degrees OD, 62 degrees OS) (differences OD and OS, p=0.001), which were similar to epilepsy control patients (mean 60 degrees OD, 61 degrees OS). Vigabatrin patients had abnormal electroretinographic photopic B wave, oscillatory, and flicker responses, which correlated with visual field constrictions. These electroretinographic responses were normal for tiagabine patients and control patients. Patients were treated with vigabatrin for a median of 46 months compared with 29 months for tiagabine. Patients taking other AEDs that may change brain GABA had normal visual function. CONCLUSION: Unlike vigabatrin, tiagabine treatment is associated with normal electroretinography and visual fields and ophthalmological function similar to epilepsy control patients. Differences between vigabatrin and other GABA modulating AEDs in retinal drug concentrations and other effects might explain why tiagabine increases in GABA reuptake do not cause retinal injury.

Adult↗

Individual state driving restrictions for people with epilepsy in the US.

BACKGROUND: States in the United States vary widely in their approaches to restricting driving for patients with epilepsy. Many states have shortened seizure-free restrictions or have adopted flexible regulations that consider individual clinical factors in determining driving privileges. The authors summarized state driving restrictions for patients with seizures, particularly unpublished regulatory practices, and determined the role and liability of physicians in judging driving safety for patients with epilepsy. METHODS: The authors surveyed motor vehicle administration bureaus in the 50 states and the District of Columbia and compared the laws, regulations, and practices restricting driving for people with epilepsy. Key responses from a questionnaire were confirmed by state motor vehicle administrations with phone interviews and by a signed executive summary. RESULTS: Twenty-eight states, including the District of Columbia, have laws requiring patients with epilepsy to be free of seizures for single fixed periods, with a median restriction of six months (range, 3 to 12 months). Twenty-three states have adopted more flexible approaches to restricting driving, such as varying seizure-free restrictions based on individual clinical factors. Many states allow patients to drive after shorter seizure-free periods than stated in their laws. These practices, however, are usually unpublished and not easily accessible. Physicians helped determine when their patients may drive in 13 states and were not legally shielded for their assessments in six of these states. CONCLUSIONS: States vary widely in how they regulate driving for patients with seizures. These varied regulatory approaches present potentially valuable models to determine how driving might be best regulated to protect public and patient safety optimally while permitting patients with controlled seizures to drive.

Accidents, Traffic↗

Suppression of post-hypoxic and post-encephalitic myoclonus with levetiracetam.

Posthypoxic and postencephalitic myoclonus is often poorly controlled with current treatments. The authors successfully treated three patients with posthypoxic and postencephalitic myoclonus by using levetiracetam, a new antiepileptic drug. Levetiracetam appears to be a promising agent for treating action myoclonus caused by hypoxic and encephalitic brain injury-the degree of functional improvement may depend on the severity of associated motor dysfunction.

Adult↗

Visual function is stable in patients who continue long-term vigabatrin therapy: implications for clinical decision making.

PURPOSE: Vigabatrin (VGB) has been shown to cause visual field constriction and other forms of mild visual dysfunction. We determined the safety of continuing VGB therapy in patients who had received prolonged treatment (>2 years) with the drug by serially monitoring changes in visual function over a 1-year period of continued therapy. We also followed up patients who discontinued VGB to see whether alternative therapies are effective. METHODS: Fifteen of 17 patients who continued VGB therapy had visual-function testing (visual acuity, color vision, kinetic and static perimetry) every 3 months for 1 year. Eighteen patients who discontinued VGB were given alternative antiepileptic drugs (AEDs); their seizure responses were measured after > or =3 months of treatment. RESULTS: Patients continuing VGB showed no worsening of visual acuity, color vision, or visual-field constriction beyond that measured in the initial test. Many patients who discontinued VGB had good seizure control with either newer or previously unsuccessful AEDs. CONCLUSIONS: For patients who have an excellent response to VGB and only mild visual changes, continued therapy may be safe with close visual monitoring. Patients who do not have a significant reduction in seizures or who experience considerable visual dysfunction with VGB may respond well to alternative therapies.

Adult↗

Human "memories" can be evoked by stimulation of the lateral temporal cortex after ipsilateral medial temporal lobe resection.

A patient with medically intractable seizures and mesial temporal sclerosis underwent a left anterior temporal lobectomy and amygdalohippocampectomy. After 4 months, his seizures recurred and a left temporal, subdural grid of electrodes was placed to localise his seizure focus. Stimulation through the grid evoked four distinct "memories", or experiential phenomena, despite absence of the ipsilateral medial temporal lobe. To our knowledge, this is the first documented case of experiential phenomena evoked by cortical stimulation in the absence of the ipsilateral medial temporal lobe.

Adult↗

Visual function loss from vigabatrin: effect of stopping the drug.

OBJECTIVE: To determine if visual function loss from vigabatrin use recovers after the drug is discontinued. BACKGROUND: Vigabatrin is an effective antiepileptic drug, but it is known to cause a variety of changes in visual function, including reductions in the visual field, visual acuity, color vision, and in electroretinogram (ERG) and electro-oculogram amplitudes. It is not known whether these changes are reversible. METHODS: Measurements of static and kinetic visual fields, visual acuity, color vision, and the ERG were recorded while patients were taking vigabatrin and again in 13 patients who had discontinued the drug because of lack of efficacy or reductions in visual field. Most of the patients had been off the drug for 3 to 6 months, although two patients had been drug-free for almost 1 year. RESULTS: Although ERG cone implicit time improved, most of the patients did not show improvement in either clinical measures of visual function (i.e., visual acuity, color vision, visual fields) or in ERG amplitudes. However, several patients who showed minimal visual field loss while on the drug had substantial recovery of ERG amplitudes. There was no statistical association between recovery of function and either duration of treatment or cumulative dosage. The multifocal ERG showed a diffuse loss of function that was not isolated to the periphery. CONCLUSIONS: Although the visual deficits in patients taking vigabatrin tend to be mild, most patients do not show improvement after they stop taking the drug. Visual field loss resulting from vigabatrin was not reversible. Visual acuity, color vision, and ERG amplitude loss may be reversible in patients with minimal or no field loss.

Adult↗

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↗

"The scarlet E": the presentation of epilepsy in the English language print media.

OBJECTIVE: To examine the coverage of epilepsy in English language newspapers and magazines to determine how they portray the medical risks associated with epilepsy, whether they report research and treatment advances accurately, whether stigmatizing biases toward persons with epilepsy persist, and to examine the sources of errors in reporting about epilepsy. BACKGROUND: The print media reflect and shape current views about epilepsy and other neurologic conditions. They also have the potential to further misconceptions about neurologic issues and particular brain disorders. Persistent myths about epilepsy, such as the ancient belief that it is a demonic disorder, can result in discrimination, emotional difficulties, and reluctance to seek effective treatment. METHODS: A large commercial database was used to search for stories about epilepsy from approximately 2,000 English language newspapers and popular magazines. Two epileptologists independently classified story themes and main sources, and screened for the presence of gross errors in 210 stories about epilepsy or seizures. The authors analyzed the metaphors and terminology used to describe seizures and epilepsy. RESULTS: The majority of English language print stories about epilepsy were accurate depictions of social and medical issues regarding the disorder, most commonly depictions of persons overcoming epilepsy and announcements of new therapies and reports of scientific advances. Thirty-one percent of the stories, however, contained gross errors, most commonly scientific inaccuracy, exaggerated treatment claims, and overestimates of the risks of dying during a seizure. New drug therapies were often described inaccurately by physicians and pharmaceutical spokespersons as curative and without side effects. Patients and their families frequently overemphasized the risk of dying during a seizure and misstated medical issues. Most celebrities with recurring seizures denied having epilepsy. Seizures were described with demonic imagery in 6% of stories. United States epilepsy associations discourage labeling patients as "epileptics"; however, the term was used in 45% of stories. CONCLUSION: Physicians and reporters should be aware of both professional and popular biases that influence the print media's presentation of the causes and consequences of epilepsy.

Anticonvulsants↗

Aggression and violence in patients with epilepsy.

Violence has been associated with epilepsy. However, the links between violent behaviors and epilepsy involve multiple factors. These range from behaviors associated with underlying brain dysfunction to postictal delirious and psychotic states and rare cases of ictal aggression. This review describes the differential diagnosis of violent acts in epilepsy and the features that can be used to evaluate these behaviors.

Journal Article↗

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Editorial↗

Visual dysfunction in patients receiving vigabatrin: clinical and electrophysiologic findings.

BACKGROUND: Vigabatrin is an antiepileptic drug that, although relatively well tolerated, is associated with visual field constriction and other visual disturbances of unclear origin. METHODS: We performed a complete neuroophthalmologic examination and electrophysiologic studies on 39 patients receiving vigabatrin and on 11 control patients. RESULTS: Nearly 50% of patients receiving vigabatrin had constricted visual fields compared with control patients. Some of the vigabatrin patients also had reduced visual acuity and abnormal color vision. In addition, most vigabatrin patients had abnormal electroretinographic results, the severity of which correlated strongly with the degree of visual field constriction. CONCLUSIONS: Vigabatrin can cause electrophysiologic evidence of retinal dysfunction and clinically detectable disturbances of visual sensory function.

Adult↗

Risk factors for seizure-related motor vehicle crashes in patients with epilepsy.

OBJECTIVE: We identified clinical risk factors for seizure-related motor vehicle crashes in patients with epilepsy. BACKGROUND: Current US laws permit epilepsy patients with controlled seizures to drive. These laws attempt to balance the important economic and social value of driving with the risk to public safety from seizure-related crashes. Various clinical factors are considered in these laws, particularly the seizure-free interval. Driving restrictions range from 3 to 18 months, however, and studies have not established how these various seizure-free intervals and other clinical factors influence the risk for seizure-related motor vehicle crashes. METHODS: We performed a retrospective case-control study to determine the influence of clinical risk factors associated with seizure-related motor vehicle crashes. Both "case" and "control" patients had epilepsy, drove, and were from the same clinic, but the cases differed in having had seizure-related crashes. RESULTS: Fifty patients with epilepsy who crashed during seizures and 50 matched control patients were compared. Factors that significantly decreased the odds of patients with epilepsy having motor vehicle crashes due to seizures were: long seizure-free intervals, reliable auras, few prior nonseizure-related accidents, and having had their antiepileptic drugs (AEDs) reduced or switched. For example, patients who had seizure-free intervals > or = 12 months had a 93% reduced odds for crashing compared to patients with shorter intervals. Other findings were: 25% of patients had more than one seizure-related crash and 20% had missed an AED dose just prior to their crash. The majority (54%) of patients who crashed were driving illegally, with seizure-free intervals shorter than legally permitted. CONCLUSION: Seizure-free intervals, the presence of reliable auras, AED therapy modifications, and a history of nonseizure-induced crashes should be considered when counseling patients with epilepsy on driving and when formulating driving regulatory policy. Case control studies of crashes due to seizures can help in assessing and monitoring such risks.

Accidents, Traffic↗

Painful stimuli evoke potentials recorded from the parasylvian cortex in humans.

Cutaneous stimulation of the face and hand with a CO2 laser in three awake patients evoked potentials (LEPs) recorded from the dominant left parasylvian cortex. These were recorded by means of a subdural grid of electrodes implanted for evaluation of epilepsy. Stimulation of the contralateral face resulted in waveforms consisting of a negative potential (N2, 162 +/- 5 ms; mean +/- SE) followed by a positive potential (P2, 340 +/- 18 ms). Both waves occurred at longer latency after hand than after facial stimulation. N2 and P2 potentials recorded from the grid correspond well in morphology to those recorded from the scalp in four additional patients tested with the same stimulation paradigm. The N2 waves recorded from the subdural grid occurred at significantly shorter latencies than did those recorded from the scalp (184 +/- 6 ms), but the P2 waves at the grid occurred at significantly longer latencies than did those recorded at the scalp (281 +/- 13 ms). The amplitudes of the potentials recorded from the grid were maximal over the parietal operculum both for contralateral stimulation of the face or hand and for ipsilateral stimulation of the face. Potentials also were recorded in this area after stimulation of the ipsilateral hand. The cortical distributions of these potentials suggest that their generators are located in the parietal operculum or in the insula, or in both, consistent with previous PET, magnetoencephalographic, and scalp LEP source analyses. These previous analyses provide indirect evidence of nociceptive input to parasylvian cortex because the interpretation of each analysis incorporates multiple assumptions. The present results are the first direct evidence of nociceptive input to the human parasylvian cortex.

Adult↗

Vigabatrin-associated retinal cone system dysfunction: electroretinogram and ophthalmologic findings.

OBJECTIVE: To determine the sources of vigabatrin-associated visual disturbances in patients treated for epilepsy. BACKGROUND: Vigabatrin is an extremely effective antiepileptic drug that selectively increases brain gamma-aminobutyric acid (GABA). Several patients recently developed constricted visual fields during vigabatrin treatment in the United Kingdom, indicating the possibility of GABA-associated retinal dysfunction. METHODS: Patients with visual symptoms treated chronically with vigabatrin at our center underwent visual evoked potentials (VEP), electroretinograms (ERG), and visual field and ophthalmologic examinations. RESULTS: Four of 38 patients treated with vigabatrin developed visual symptoms 2 to 40 months after starting the drug. Two patients complained of constricted visual fields and two had blurred vision. ERG demonstrated evidence of bilateral retinal dysfunction consistent with reduced inner retinal cone response in all four patients. Oscillatory potential responses were lost, suggesting impairment of the highly GABAergic amacrine cells. Two of the patients had normal VEPs and minimal findings on clinical ophthalmology examinations despite abnormal ERGs. Abnormal examination findings were narrowed retinal arteries, surface wrinkling retinopathy, and abnormal macular reflexes. One patient also had reduced rod photoreceptor function in the more symptomatic left eye. CONCLUSIONS: Visual field constriction and blurring during vigabatrin therapy is associated with retinal cone system dysfunction. Visual symptoms may represent selective vulnerability of retinas of affected patients to GABAergic effects of vigabatrin. The prevalence and course of retinal changes associated with vigabatrin therapy are important to determine in a larger group of patients.

Adult↗

Tiagabine therapy for complex partial seizures. A dose-frequency study. The Tiagabine Study Group.

OBJECTIVE: To evaluate the efficacy and safety of 2 regimens of tiagabine as add-on therapy for patients with complex partial seizures (CPSs) that are refractory to other treatment. DESIGN: Randomized, double-blind, placebo-controlled, add-on, parallel-group trial with an 8-week baseline period, 12-week experimental period (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week termination period. SETTING: Twenty-six centers throughout the United States. PATIENTS: Three hundred fifty-one patients were enrolled, 318 were entered in the double-blind period, and 271 completed the study. INTERVENTIONS: Tiagabine, 16 mg 2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the fixed dose. MAIN OUTCOME MEASURE: The median change in the 4-week rate of CPSs from baseline to experimental period. RESULTS: The median change from baseline was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2 times per day, and it was -1.2 CPSs in the group of patients who were given tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the patients who were given tiagabine 2 times per day and in 27% of the patients who were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P < or = .001 for each tiagabine-treated group compared with the placebo group). The most frequent adverse events involved the central nervous system and occurred in comparable proportions in the 3 treatment groups. Similar proportions of patients discontinued the study prematurely for adverse events. CONCLUSIONS: Tiagabine administered 2 and 4 times daily as add-on pharmacotherapy was effective in reducing CPSs in patients with epilepsy whose conditions were refractory to treatment with other antiepileptic agents, and it was well tolerated.

Adolescent↗