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Biomedical subjects

Orrin Devinsky

Publications and source records attributed to Orrin Devinsky.

At least 19 recordsLinked to original sources
PubMed2026

Valproate vs levetiracetam in juvenile myoclonic epilepsy: systematic review and meta-analysis.

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome with onset typically in adolescence and a chronic course requiring long-term antiseizure medications (ASMs). Valproate (VPA) is the most effective treatment for seizure control in JME but use is limited by metabolic, cognitive, and teratogenic adverse effects (AEs). Levetiracetam (LEV) is an alternative ASM when VPA is contraindicated or not tolerated. Comparisons of the efficacy and long-term tolerability of VPA and LEV remain limited. METHODS: We conducted a systematic review and meta-analysis using PRISMA guidelines and the Cochrane Handbook. We searched PubMed, Embase, and the Cochrane Library from inception through January 2026 for studies in JME patients comparing LEV and VPA, and included randomized controlled trials and comparative observational studies with ≥ 6 months of follow-up. Primary outcomes were seizure remission and ASM failure or treatment discontinuation. Secondary outcomes included, memory impairment, weight gain or obesity, dizziness, and overall AEs. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was assessed using the I2 statistic. RESULTS: Seven studies encompassing 1,009 patients were included. VPA was associated with higher pooled seizure remission rates compared with LEV (344 of 574 vs. 169 of 390; RR 1.44, 95% CI 1.27-1.63); however, substantial heterogeneity (I2 = 88.4%) limits confidence in this finding. VPA was associated with a lower risk of drug failure or treatment discontinuation (RR 0.68, 95% CI 0.54-0.86), with no heterogeneity (I2 = 0.0%). VPA was also associated with a higher risk of memory impairment (RR 5.37, 95% CI 2.05-14.04; I2 = 74.5%) and weight gain or obesity (RR 6.40, 95% CI 3.64-11.26; I2 = 35.9%). No significant differences were observed between treatments regarding dizziness (RR 0.91, 95% CI 0.61-1.37; I2 = 21.2%). Sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSION: VPA was associated with higher seizure remission rates and lower treatment discontinuation compared with LEV; however, these findings must be interpreted with caution given the substantial heterogeneity, the predominance of observational studies, and the serious risk of bias identified in most included studies VPA also demonstrated lower rates of treatment discontinuation, despite a higher burden of cognitive impairment and weight gain. No relevant differences were observed regarding dizziness. Large-scale randomized trials with standardized outcome definitions and longer follow-up are needed to define the comparative risk-benefit profiles of LEV and VPA in JME.

Humans↗
PubMed2026

Add-on treatment with vinpocetine reduces seizure frequency and improves comorbidities in patients with loss-of-function γ-aminobutyric acid type A receptor variants.

OBJECTIVE: The semisynthetic compound vinpocetine has gained attention as a potential precision medicine for developmental and epileptic encephalopathies caused by loss-of-function (LoF) variants in γ-aminobutyric acid type A (GABAA) receptor genes. As a positive allosteric modulator of GABAA receptors, case reports suggest that vinpocetine can reduce epileptiform activity and seizure frequency, while improving cognitive function in patients with GABAA receptor-related epilepsies. Here, we extend these observations with a retrospective observational study evaluating the response to vinpocetine in an additional seven patients. METHODS: Patients initiated treatment with vinpocetine between 2018 and 2025 at the Danish Epilepsy Centre or abroad. Clinical data were collected from medical records, seizure diaries, and neuropsychological assessments. The modulatory efficacy of vinpocetine was investigated using electrophysiological studies. RESULTS: Nine patients harboring eight GABAA receptor LoF variants were given add-on vinpocetine treatment. Electrophysiological analyses confirmed dose-dependent positive modulation by vinpocetine across tested variants. Six patients with a median age of 15.5 years (range = 6-29) continued treatment for a median of 24 months (range = 12-90), whereas three discontinued due to adverse effects (AEs) or lack of efficacy. The patients' level of function ranged from normal to moderate intellectual disability, psychiatric comorbidities, and behavioral disturbances. Four patients initiated vinpocetine due to uncontrolled seizures. One became seizure-free, and two experienced a 50%-55% reduction. Electroencephalograms demonstrated improved spike-wave indexes in four patients. Six showed improvement in nonseizure factors, and caregivers reported reduced aggressivity and better vocabulary in one. Vinpocetine was well tolerated, with only mild and reversible AEs reported. SIGNIFICANCE: Adjunctive vinpocetine shows promise as a targeted therapy for patients with GABAA receptor LoF variants, decreasing seizure frequency and positively impacting nonseizure factors, with only mild AEs reported. Vinpocetine may be a safe and effective therapy for patients with GABAA receptor-related epilepsies, which should be investigated further in future N-of-1 trials.

Humans↗
PubMed2003

Primary generalized epilepsy: a risk factor for seizures in labor and delivery?

PURPOSE: Women in the United States who have epilepsy give birth to about 20000 newborns every year. Because seizures during late gestation and delivery may seriously affect the fetus, and because primary generalized tonic-clonic (GTC) seizures may occur during labor and delivery in 1-2% of women with epilepsy, we attempted to define the rate, risks, and causes of seizures during labor and delivery. METHODS: To characterize seizures during labor and delivery, we retrospectively analyzed 89 consecutive pregnancies of women with epilepsy on antiepileptic drugs (AEDs). Six epileptologists in our group had treated these patients. We confirmed data and acquired new information by telephone for 83.1% of the pregnancies, and categorized the women as having primary generalized or partial epilepsy. Most of the patients (78%) were on monotherapy during pregnancy; 20% took two AEDs, and 3% took three AEDs during that period. RESULTS: Seizures during labor and delivery occurred in 4/32 (12.5%) patients with primary generalized epilepsy, but in none of the 57 women with partial epilepsy (P<0.05). None of the 38 patients with therapeutic AED levels before labor and delivery had seizures, compared to 3/37 (8.1%) of the subtherapeutic group. However, drug levels were taken at variable times in relation to delivery, limiting their value. Also, the levels sampled were both total and free levels; the latter would be more helpful to determine the adequacy of AED drug coverage. CONCLUSIONS: Maintaining therapeutic AED levels during the last trimester may help prevent seizures during labor and delivery, especially in women with generalized epilepsy. Women with epilepsy who had subtherapeutic AED levels and had been seizure-free may be at-risk for seizures during labor and delivery. Our sample was small, and a random sampling bias may have affected the results.

Adult↗
PubMed2003

A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials.

This report reviews behavioral adverse events occurring among adults receiving levetiracetam (LEV) or placebo who participated in short-term, placebo-controlled studies in epilepsy (1023), cognitive disorders (719), or anxiety disorders (1510) and epilepsy patients (1393) observed in long-term trials. Behavioral events (affective, psychotic, and suicidal symptoms) were significantly more common among epilepsy patients than cognition or anxiety patients treated with LEV for similar durations (P=0.022). Affective symptoms occurring at 1% or more often in epilepsy placebo-controlled trials included depression (3.8% LEV-2.1% placebo), nervousness (3.8%-1.8%), hostility (2.3%-0.9%), anxiety (1.8%-1.1%), and emotional lability (1.7%-0.2%). Patients with cognitive and anxiety disorders had lower incidences of these symptoms. The incidence of behavioral events in LEV-treated epilepsy patients was lower than rates reported for some other antiepileptic drugs. These data support the hypothesis that some feature related to epilepsy is the cause of many behavioral events rather than the addition of a specific antiepileptic drug.

Humans↗
PubMed2003

Psychogenic, nonepileptic seizures associated with video-EEG-verified sleep.

PURPOSE: Nonepileptic seizures (NES) are expressions of a psychiatric disease state, usually conversion disorder, that mimic epileptic seizures (ES) but are not associated with the neurophysiologic changes of epilepsy. Conversion has not been demonstrated to emerge from the sleeping state. Emergence out of sleep is usually considered a virtual exclusion criterion for NES, signifying the presence instead of ES. We sought to test this hypothesis. METHODS: We retrospectively reviewed the video-EEG of all patients admitted to our epilepsy unit over a 3-year period, who were suspected of manifesting NES. We examined the relation between NES and the patients' sleep/wake state in this cohort. Two epileptologists blindly reviewed an intermixture of cases suspected to represent NES emerging out of sleep, together with control cases. Classification of each case was made independently. RESULTS: We found that in a small minority of patients (<1%), NES began either while the patient was sleeping, or within several seconds of arousal, well before a plan to simulate a seizure could likely have been formulated in the wakeful state. CONCLUSIONS: In some cases, NES are not the product of the awake mind, but rather represent a psychiatric condition that can be manifest in sleep.

Adult↗
PubMed2003

Stratifying differences on ictal/interictal subtraction SPECT images.

PURPOSE: Subtraction of interictal from ictal single-photon emission computed tomography (SPECT) yields numerous foci that encompass a range of pixel values scattered in the brain. This preliminary study evaluated the significance of this range of values. METHODS: Subtraction images were obtained by registering, normalizing, and subtracting interictal from ictal SPECT for 13 patients. Pixel values of the resulting foci were divided into two groups: group I with 75-100% and group II with 50-75% of the maximal pixel value. Locations of these foci were determined, and concordance with surgical outcomes and scalp and invasive EEG findings was evaluated. RESULTS: In 10 of 13 cases, group I foci showed good concordance with ictal scalp EEG. In addition, group I foci corresponded well to invasive EEG findings in nine of 10 cases. Group I foci had bilateral distributions in seven of 13 cases. In 10 of 13 cases, group I foci corresponded well to regions of surgical resection. Of these 10 patients, nine showed good concordance with scalp EEG, eight showed good invasive EEG concordance, and eight were seizure free after resection. Conversely, group II foci had good concordance with ictal scalp EEG in only five of 13 cases, and invasive EEG findings, in only five of 10 cases. Group II foci had bilateral distributions in 10 of 13 cases. All 10 cases underwent unilateral surgical resections, and all had good surgical outcomes. In six of 13 cases, group II foci showed concordance with surgical sites. Of these six foci, four had poor concordance with scalp EEG, one had poor concordance with invasive EEG, and five had good surgical outcomes. Sensitivity and specificity for seizure localization of Group I foci were 40% and 88% respectively while sensitivity and specificity of Group II foci were 20% and 79% respectively. CONCLUSIONS: Our data demonstrate that foci with 75-100% of maximal pixel values show good concordance with seizure foci, whereas foci of 50-75% may not. Therefore stratifying ictal/interictal differences may improve the specificity and localizing value of subtraction SPECT.

Adolescent↗
PubMed2003

Surgical treatment of multifocal epilepsy involving eloquent cortex.

PURPOSE: This report describes our long-term follow-up for combined resective surgery and multiple subpial transections (MSTs) in patients with refractory epilepsy involving eloquent and noneloquent cortex in multiple lobes. Multiple independent seizure foci made these patients poor candidates for conventional surgery. METHODS: MST and resective surgery were used in 13 patients to treat localization-related refractory epilepsy involving eloquent and noneloquent cortex of two or more lobes. Preoperative investigation was followed by invasive monitoring. RESULTS: Eleven patients had MST plus resection involving two different lobes, and two patients had MST plus resection involving three different lobes. MSTs were performed on the primary sensorimotor cortex (eight patients), temporal language area (two patients), Broca's area (one patient), and on both frontal motor and temporal language areas (two patients). Nine patients had a two-stage procedure, and four patients had a three-stage procedure (two consecutive subdural grid studies followed by resections). Average follow-up was 59.2 months (range, 42-98 months). With a modified Engel Outcome Scale, four patients (31%) had a class I outcome; three (23%), class II; three (23%), class III; and three (23%), class IV. Ten (77%) patients had a >50% reduction of seizure burden. CONCLUSIONS: Combined MST and resection can meaningfully improve seizure control in patients with multifocal epilepsy involving eloquent cortex. Prospective randomized studies are needed.

Adolescent↗
PubMed2002

Cognition-induced epilepsy.

Cognition-induced epilepsy comprises a group of loosely tied syndromes characterized by seizures regularly precipitated by cognitive tasks. Linguistic operations (e.g., reading, writing) and decision making associated with visuospatial manipulation are the most frequent and best-characterized triggers. The syndromes reviewed have a high degree of overlap and clinical/EEG variability, suggesting that any of the neural networks subserving these complex tasks may promote seizures on either a topographic basis or a functional/connective basis. Treatment options include typical pharmacological and surgical interventions as well as stimulus alteration, threshold alteration, and avoidance conditioning. We postulate that more commonly encountered epilepsy syndromes also have complex triggers.

Journal Article↗
PubMed2002

Psychiatric uses of antiepileptic treatments.

Antiepileptic drugs (AEDs) possess potent negative or positive psychotropic effects. Clear evidence of benefit exists for valproate, carbamazepine, and lamotrigine in bipolar disorder. Reports of benefit from various AEDs in mood, anxiety, impulse control, and personality disorder are reviewed. Further research is needed to clarify which patients are likely to benefit. Clinicians must closely attend to the ongoing risk/benefit analysis and consider possible iatrogenic worsening of neuropsychiatric symptoms.

Journal Article↗
PubMed2002

Treatment of nonepileptic seizures.

Studies on nonepileptic seizures (NES) provide dichotomous data sets: extensive observational findings, but a paucity of controlled treatment data. Psychosocial stressors, whose full impact may lie outside a patient's awareness, often underlie NES. These stressors, along with patient's learned patterns of coping, may bring forth or potentiate comorbid psychiatric disorders. Patients with NES often have dysfunction in emotion regulation and family dynamics, as well as unemployment/disability. High percentages of comorbid disorders such as major depressive disorder, post-traumatic stress disorder, and cluster B personality with impulsivity (all disorders associated with serotonin system function) also exist in the NES population. The preliminary observational evidence suggests that specific psychotherapies and pharmacotherapy directed at comorbid conditions may be the most effective treatment for NES.

Journal Article↗
PubMed2002

Multiple subpial transection for intractable partial epilepsy: an international meta-analysis.

PURPOSE: Because the number and variety of patients at any single facility is not sufficient for clinical or statistical analysis, data from six major epilepsy centers that performed multiple subpial transections (MSTs) for medically intractable epilepsy were collected. METHODS: A meta-analysis was performed to elucidate the indications and outcome, and to assess the results of the procedure. Overall, 211 patients were represented with data regarding preoperative evaluation, procedures, seizure types and frequencies before and after surgery, postoperative deficits, and demographic information. Fifty-three patients underwent MST without resection. RESULTS: In patients with MST plus resection, excellent outcome (>95% reduction in seizure frequency) was obtained in 87% of patients for generalized seizures, 68% for complex partial seizures, and 68% for simple partial seizures. For the patients who underwent MST without resection, the rate of excellent outcome was only slightly lower, at 71% for generalized, 62% for complex partial, and 63% for simple partial seizures. EEG localization, age at epilepsy onset, duration of epilepsy, and location of MST were not significant predictors of outcome for any kinds of seizures after MST, with or without resection. New neurologic deficits were found in 47 patients overall, comparable in MST with resection (23%) or without (19%). CONCLUSIONS: These preliminary results suggest that MST has efficacy by itself, with minimal neurologic compromise, in cases in which resective surgery cannot be used to treat uncontrolled epilepsy. MST should be investigated as a stand-alone procedure to allow further development of criteria and predictive factors for outcome.

Epilepsies, Partial↗
PubMed2002

Epilepsy in The Alienist and Neurologist, 1880-1920.

PURPOSE: To study the history of epilepsy from 1880 to 1920. METHODS: We reviewed all 40 volumes of The Alienist and Neurologist and identified articles concerning primarily epilepsy. We analyzed three of these articles in greater detail. RESULTS: The Alienist and Neurologist published "Original Contributions,""Selections," (abstracts from other journals written by the editorial board), "Editorials," and (book) "Reviews." Of 258 epilepsy articles, there were 40 Original Contributions, 164 Selections, 39 Editorials, and 15 Reviews. These articles included 71 on therapy (41 medication, 13 surgery, and 17 other therapies); 66 general discussions; 46 on etiology or symptoms; 34 case studies; 28 social/legal articles; and 13 autopsy or pathology articles. CONCLUSIONS: Analysis of The Alienist and Neurologist provides a unique and valuable perspective on the clinical practice and academic world of epileptology during the decades around the turn of the twentieth century.

Epilepsy↗
PubMed2002

What do you do when they grow up? Approaches to seizures in developmentally delayed adults.

Epilepsy and developmental disabilities (DD) often occur together but affect individuals differently and have a complex causal relationship. Most epilepsy in the population with DD is partial or symptomatic generalized. Seizures and antiepileptic drugs (AEDs) can further delay development, and the DD can complicate treatment and adjustment to epilepsy. Medical care and decision making require careful coordination of health care providers and the family, especially because of the trend for the patients to live in group homes. Behavioral and psychiatric disorders are difficult to diagnose but common in those with DD and epilepsy; psychiatric disorders are perhaps up to sevenfold higher in this group than in the general population. Psychotropic medications-antidepressants, anxiolytics (but use caution with benzodiazepines), antipsychotics, and stimulants-are appropriate for those with psychiatric disorders. Diagnostic difficulties may lead to undertreatment, and the motivation to lessen certain behaviors may lead to overtreatment. Because those with DD may be unusually sensitive to adverse effects of both seizures and AEDs, cognitive and behavioral side effects must be carefully monitored. Few relevant studies exist. For some patients, comorbid psychiatric disorders may be treated with one AED, such as carbamazepine, lamotrigine, or valproate. Phenobarbital and phenytoin may be inappropriate for those with epilepsy and DD. Studies have shown some success with oxcarbazepine (for partial and generalized epilepsy) and with adjunctive lamotrigine. For those on medication regimens, perhaps taking combinations of drugs for numerous years, queries about earlier attempts to reduce AEDs and gradual efforts to substitute less toxic mediations are worthwhile. Vagus nerve stimulation and epilepsy surgery for those with medically refractory epilepsy may be options after careful evaluation.

Adult↗
PubMed2002

Epilepsy surgery in tuberous sclerosis: multistage procedures with bilateral or multilobar foci.

Refractory seizures are common in patients with tuberous sclerosis and can contribute to developmental delay and behavioral problems. Surgical intervention can reduce the seizure burden in selected patients with tuberous sclerosis and refractory epilepsy, thereby improving cognitive function, behavior, and quality of life. However, the risks of surgery are usually considered unacceptable when the epileptogenic focus lies over dominant hemisphere eloquent cortex or is multilobar. Multistage invasive monitoring can provide detailed data regarding the location and number of ictal foci and functional extraoperative mapping can precisely delineate the boundaries of eloquent areas of the brain. If independent ictal onsets are demonstrated, a staged surgical approach can allow a more aggressive yet safe procedure in selected patients. A combination of staged resection and multiple subpial transections may provide an opportunity to treat epileptogenic foci located over eloquent cortex. Bilateral staged resections can be used when independent bihemispheric foci are present in patients with tuberous sclerosis. This article presents two cases, one of which (case 2) was previously reported, on successful multistage surgical treatment of epileptogenic foci located over an eloquent cortex or in both hemispheres in children with tuberous sclerosis. This case is represented since there is additional follow-up available and the prior report was to a neurosurgical audience. This multistage approach permitted resection of epileptogenic foci that would traditionally have been considered inoperable.

Child↗
PubMed2002

Evaluation of a first seizure. Is it epilepsy?

The first step in evaluation of a presumed seizure is to determine whether the event was indeed a seizure and which diagnostic studies are needed. The second step is to correctly diagnose the seizure on the basis of the medical history and findings from the physical, neurologic, and laboratory evaluation. The third step is to decide whether drug treatment is necessary. Every paroxsymal event is unique, and not every seizure needs to be treated. When treatment is deemed appropriate, an antiepileptic drug should be chosen after discussion with the patient and consideration of the risk-benefit profile of the available agents.

Anticonvulsants↗
PubMed2002

Epilepsy.

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Anticonvulsants↗